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Cited by 645Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsPharmacology and Nanomedicine Research

Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles

Open access
Singh, Akhand Pratap, Biswas, Arpan, Shukla, Aparna, Maiti, Pralay·2019·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-019-0068-3PMC PMC6799838
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Abstract

The application of nanomedicines is increasing rapidly with the promise of targeted and efficient drug delivery. Nanomedicines address the shortcomings of conventional therapy, as evidenced by several preclinical and clinical investigations indicating site-specific drug delivery, reduced side effects, and better treatment outcome. The development of suitable and biocompatible drug delivery vehicles is a prerequisite that has been successfully achieved by using simple and functionalized liposomes, nanoparticles, hydrogels, micelles, dendrimers, and mesoporous particles. A variety of drug delivery vehicles have been established for the targeted and controlled delivery of therapeutic agents in a wide range of chronic diseases, such as diabetes, cancer, atherosclerosis, myocardial ischemia, asthma, pulmonary tuberculosis, Parkinson’s disease, and Alzheimer’s disease. After successful outcomes in preclinical and clinical trials, many of these drugs have been marketed for human use, such as Abraxane®, Caelyx®, Mepact®, Myocet®, Emend®, and Rapamune®. Apart from drugs/compounds, novel therapeutic agents, such as peptides, nucleic acids (DNA and RNA), and genes have also shown potential to be used as nanomedicines for the treatment of several chronic ailments. However, a large number of extensive clinical trials are still needed to ensure the short-term and long-term effects of nanomedicines in humans. This review discusses the advantages of various drug delivery vehicles for better understanding of their utility in terms of current medical needs. Furthermore, the application of a wide range of nanomedicines is also described in the context of major chronic diseases.

AI snapshot

Written from the paper’s full text.

TL;DR

This review surveys nanomaterial-based drug delivery vehicles—liposomes, nanoparticles, hydrogels, micelles, dendrimers, mesoporous materials, and scaffolds—for targeted and controlled therapy in chronic diseases including diabetes, neurodegenerative disease, cardiovascular disease, respiratory disease, tuberculosis, and cancer. It highlights preclinical and clinical examples and marketed nanomedicines, while stressing that extensive clinical trials, standardized dosing, toxicology, and regulatory frameworks are still needed.

Key findings

  • Nanocarriers can improve site-specific delivery, sustained release, bioavailability, and reduce side effects across chronic diseases; marketed examples include Abraxane®, Caelyx®, Mepact®, Myocet®, Emend®, and Rapamune®.
  • In diabetes, TMC-CSK-INS nanoparticles produced maximum blood glucose depression of ~28% at 3 h versus ~20% for TMC-INS; vitamin B12-coupled dextran nanoparticles reduced blood glucose ~70–75% for 54 h in diabetic rats and 60% at 20 h in diabetic mice.
  • In neurological disease, rivastigmine-loaded PBCA-80 nanoparticles showed 3.82-fold higher brain uptake than free drug; galantamine SLNs had ~83% entrapment, >90% release in 24 h, and two-fold higher bioavailability; curcumin-loaded lactoferrin-functionalized nanolipid carriers enhanced brain uptake 2.78-fold; miR-124 nanoparticles increased mature neurons 2.5-fold in a Parkinson’s disease model.
  • In respiratory/TB/cancer applications, montelukast-loaded nanostructured lipid carriers improved bioavailability 12-fold; mannose-coated SLNs enhanced rifabutin cellular uptake up to six-fold; liposomal ciprofloxacin had 90% loading efficiency with up to 30% remaining after nebulization; 90 nm liposomes escaped leaky tumor vasculature but did not permeate away from the tumor for a week.

Methods

  • Narrative review; no systematic search strategy, databases, inclusion/exclusion criteria, or quantitative synthesis are stated.
  • Synthesizes preclinical and clinical literature on nanomaterial-based drug delivery vehicles and their applications across chronic diseases, including marketed nanomedicines.
  • Main analysis is descriptive and thematic, organized by carrier type and disease area.

Limitations

  • The paper states that clinical translation remains a major challenge requiring many well-defined clinical trials; the one-size-fits-all approach is a drawback; dosage standardization, extensive toxicology, short- and long-term side-effect assessment, new regulatory frameworks, and scalable, cost-effective, reproducible manufacturing are needed.
  • Evident from the text: as a narrative review, it does not systematically assess study quality or risk of bias, and many cited therapeutic results come from preclinical animal or cell models rather than human trials.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41392-019-0068-3

Cites

262 of 262 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 235 cited sources checked · 0 supported · 0 flagged

  • Interpretationnone given

    A variety of drug delivery vehicles have been established for targeted and controlled delivery of therapeutic agents in diabetes, cancer, atherosclerosis, myocardial ischemia, asthma, pulmonary tuberculosis, Parkinson's disease, and Alzheimer's disease.

    “A variety of drug delivery vehicles have been established for the targeted and controlled delivery of therapeutic agents in a wide range of chronic diseases, such as diabetes, cancer, atherosclerosis, myocardial ischemia, asthma, pulmonary tuberculosis, Parkinson’s disease, and Alzheimer’s disease.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Efficacy of drug delivery vehicles depends on their size, shape, hydrophobicity, surface parameters, and other chemical and biophysical features.

    “However, the efficacy of these drug delivery vehicles depends on their size, shape, hydrophobicity, surface parameters, and several other chemical and biophysical features.6,7”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [6] Patel, D. K. et al. Influence of graphene on self-assembly of polyurethane and evaluation of its biomedical properties. Polymer 65, 183–192 (2015). source

      Not checked in the free run.

    • cites [7] Senapati, S., Mahanta, A. K., Kumar, S. & Maiti, P. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct. Target. Ther. 3, 7 (2018). source

      Not checked in the free run.

  • Premisecitation

    A wide variety of organic, inorganic, polymeric and metallic nanostructures are frequently used as targeted and controlled drug delivery vehicles.

    “A wide variety of organic, inorganic, polymeric and metallic nanostructures, including dendrimers, micelles, solid lipid nanoparticles (SLNs), carbon nanotubes, and liposomes, are frequently used as targeted and controlled drug delivery vehicles.3–5”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Singh, N. K. et al. CNT Induced β-phase in polylactide: unique crystallization, biodegradation, and biocompatibility. J. Phys. Chem. C. 117, 10163–10174 (2013). source

      Not checked in the free run.

    • cites [4] Lombardo, D., Kiselev, M. A. & Caccamo, M. T. Smart nanoparticles for drug delivery application: development of versatile nanocarrier platforms in biotechnology and nanomedicine. J. Nanomater. 2019, 3702518 (2019). source

      Not checked in the free run.

    • cites [5] Mishra, A. et al. Self-assembled aliphatic chain extended polyurethane nanobiohybrids: Emerging hemocompatible biomaterials for sustained drug delivery. Acta Biomater. 10, 2133–2146 (2014). source

      Not checked in the free run.

  • Premisecitation

    A substantial number of preclinical and clinical studies suggest suitability of nanoparticles, liposomes, micelles, and dendrimers for treatment of various diseases.

    “A substantial number of preclinical and clinical studies suggest their suitability for the treatment of various diseases.20–22”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [20] Kapusetti, G. et al. Bone cement based nanohybrid as a super biomaterial for bone healing. J. Mater. Chem. B 2, 3984–3997 (2014). source

      Not checked in the free run.

    • cites [21] Sharma, A. & Sharma, U. S. Liposomes in drug delivery: progress and limitations. Int. J. Pharm. 154, 123–140 (1997). source

      Not checked in the free run.

    • cites [22] Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R. & Rudzinski, W. E. Biodegradable polymeric nanoparticles as drug delivery devices. J. Control. Release 70, 1–20 (2001). source

      Not checked in the free run.

  • Premisecitation

    Metformin-loaded niosomes have better efficacy than pure metformin in reducing blood glucose levels.

    “Pharmacokinetic testing confirmed the better efficacy of metformin-loaded niosomes over pure metformin in reducing blood glucose levels.84”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [84] Hasan, A. A., Madkor, H. & Wageh, S. Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system. Drug Deliv. 20, 120–126 (2013). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. 23
  • May combine two claims. 98

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Peptides, nucleic acids (DNA and RNA), and genes have shown potential as nanomedicines for treatment of several chronic ailments.

    “Apart from drugs/compounds, novel therapeutic agents, such as peptides, nucleic acids (DNA and RNA), and genes have also shown potential to be used as nanomedicines for the treatment of several chronic ailments.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Nanomedicines provide site-specific drug delivery, reduced side effects, and better treatment outcome compared with conventional therapy.

    “Nanomedicines address the shortcomings of conventional therapy, as evidenced by several preclinical and clinical investigations indicating site-specific drug delivery, reduced side effects, and better treatment outcome.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Nanometer-sized materials with high biocompatibility and biodegradability are considered excellent drug delivery systems for biomedical applications.

    “Ideally, nanometer-sized materials with high biocompatibility8 and biodegradability9 are considered excellent drug delivery systems for biomedical applications.10”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Kohane, D. S. & Langer, R. Biocompatibility and drug delivery systems. Chem. Sci. 1, 441–446 (2010). source

      Not checked in the free run.

    • cites [9] Mahapatro, A. & Singh, D. K. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. J. Nanobiotechnology 9, 55 (2011). source

      Not checked in the free run.

    • cites [10] Maiti, P., Senapati, S. & Saraf, S. Inhibition of Chronic Osteomyelitis using Sustained Release of Drug from Biodegradable Polymeric Chip. Clin. Oncol. 3, 1406 (2018).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Liposomes are generally biocompatible, biodegradable, nontoxic, and able to entrap lipophilic and hydrophilic drugs for site-specific drug delivery.

    “They are generally biocompatible, biodegradable, nontoxic, and able to entrap lipophilic and hydrophilic drugs for site-specific drug delivery.77,78”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [77] Allison, S. D. Liposomal drug delivery. J. Infus. Nurs. 30, 89–95 (2007). source

      Not checked in the free run.

    • cites [78] Maurer, N., Fenske, D. B. & Cullis, P. R. Developments in liposomal drug delivery systems. Expert Opin. Biol. Ther. 1, 923–947 (2001). source

      Not checked in the free run.

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    Premisecitation

    Drug-loaded nanofibers significantly lower blood glucose level in diabetic male Wistar rats and show better efficiency in controlling diabetes than commercial formulation.

    “The in vivo study confirmed the effectiveness of the drug-loaded nanofibers, as a significant lowering of the blood glucose level was observed in diabetic male Wistar rats. Furthermore, the patch showed better efficiency in controlling diabetes than did the commercial formulation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Sharma, A. et al. Electrospun composite nanofiber-based transmucosal patch for anti-diabetic drug delivery. J. Mater. Chem. B 1, 3410–3418 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Scaffolds are employed in position of natural fibrous collagen during bone tissue engineering, playing vital role in bone regeneration by regulating cell adhesion, proliferation, and differentiation.

    “Scaffolds are employed in the position of natural fibrous collagen during bone tissue engineering, which plays a vital role in bone regeneration by regulating cell adhesion, proliferation, and differentiation.61”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Ma, P. X. & Zhang, R. Synthetic nano‐scale fibrous extracellular matrix. J. Biomed. Mater. Res. 46, 60–72 (1999). source

      Not checked in the free run.

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    Premisecitation

    Size of chitosan nanoparticles increased from 182 to 342 nm after modification with TMC, CSK, and INS, and zeta potential decreased from 10 to 3 mV.

    “The size of the nanoparticle was increased from 182 to 342 nm after the nanoparticles were modified with TMC, CSK, and INS, which decreased the zeta potential from 10 to 3 mV.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [86] Jin, Y. et al. Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport. Biomaterials 33, 1573–1582 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Liposome with lipid:cholesterol ratio 3:1 shows maximum insulin trapping efficiency along with good membrane fluidity and minimum insulin leakage.

    “The liposome with a lipid:cholesterol ratio of 3:1 shows maximum insulin trapping efficiency along with good membrane fluidity and minimum insulin leakage from internal aqueous components.79”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] Zhang, X. et al. Enhanced hypoglycemic effect of biotin-modified liposomes loading insulin: effect of formulation variables, intracellular trafficking, and cytotoxicity. Nanoscale Res. Lett. 9, 185 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Polymeric nanoparticles are able to encapsulate both hydrophilic and hydrophobic drugs and bind macromolecules such as proteins, antibodies or nucleic acids.

    “As a result, these nanoparticles are able to encapsulate both hydrophilic and hydrophobic drugs as well as to bind macromolecules, such as proteins, antibodies or nucleic acids.46”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Elsabahy, M. & Wooley, K. L. Design of polymeric nanoparticles for biomedical delivery applications. Chem. Soc. Rev. 41, 2545–2561 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Insulin-loaded PVA-alginate composite nanofiber patch shows sustained and controlled release of insulin in vitro, with ~100% drug release within 12 h following first-order kinetics with initial burst.

    “The in vitro drug release study confirmed a sustained and controlled release pattern of the insulin from the nanofiber (Fig. 2a) and ~100% drug release from the patch occurred within 12 h. The release pattern follows first-order kinetics with an initial burst release of the drug.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Sharma, A. et al. Electrospun composite nanofiber-based transmucosal patch for anti-diabetic drug delivery. J. Mater. Chem. B 1, 3410–3418 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Stealth liposomes have been used successfully in delivery of doxorubicin for treatment of solid tumors and are marketed as Doxil or Caelyx.

    “Stealth liposomes have been used successfully in the delivery of doxorubicin for the treatment of solid tumors and are presently marketed as ‘Doxil’ or ‘Caelyx’.54”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Immordino, M. L., Dosio, F. & Cattel, L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int. J. Nanomed. 1, 297 (2006). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chitosan-coated liposomes facilitate insulin delivery, and hypoglycemic efficacy increases with increasing chitosan molecular weight.

    “In an alternative approach, chitosan-coated liposomes facilitate insulin delivery, and the hypoglycemic efficacy increases with increasing chitosan molecular weight.80”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [80] Wu, Z., Ping, Q., Wei, Y. & Lai, J. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice. Acta Pharmacologica Sin. 25, 966–972 (2004).

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Nanomedicines are emerging as a novel strategy to overcome the blood-brain barrier and provide targeted and sustained release for neurodegenerative diseases.

    “However, nanomedicines are emerging as a novel strategy to overcome the BBB and to provide the advantage of targeted and sustained release.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The inability or limited ability of currently available drug molecules to cross the blood–brain barrier is the major reason for their limited therapeutic effects in neurodegenerative diseases.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    AChE inhibitors improve postsynaptic stimulation by maintaining levels of acetylcholine.

    “AChE inhibitors improve postsynaptic stimulation by maintaining the levels of acetylcholine.98”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Bentley, P., Driver, J. & Dolan, R. J. Modulation of fusiform cortex activity by cholinesterase inhibition predicts effects on subsequent memory. Brain 132, 2356–2371 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PEGylated nanoliposomes and SLNs loaded with galantamine and memantine showed increased brain-targeted delivery with neuroprotective properties.

    “PEGylated nanolipsomes and SLNs loaded with galantamine105 and memantine106 showed increased brain-targeted delivery with neuroprotective properties.106”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [105] Mufamadi, M. S. et al. Ligand-functionalized nanoliposomes for targeted delivery of galantamine. Int. J. Pharm. 448, 267–281 (2013). source

      Not checked in the free run.

    • cites [106] Laserra, S. et al. Solid lipid nanoparticles loaded with lipoyl–memantine codrug: preparation and characterization. Int. J. Pharm. 485, 183–191 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Curcumin-loaded lactoferrin-functionalized nanolipid carriers enhanced brain uptake by 2.78-fold and could recover hippocampal damage in AD animal model.

    “In another study, curcumin-loaded lactoferrin-functionalized nanolipid carriers enhanced brain uptake by 2.78-fold and could recover hippocampal damage in the AD animal model.112”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Meng, F. et al. A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer’s disease. Colloids Surf. B: Biointerfaces 134, 88–97 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Maximum drug entrapment of galantamine SLNs was ~83%, with greater than 90% drug release in 24 h.

    “The maximum drug entrapment of these SLNs was ~83 %, with greater than 90% drug release in 24 h.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [104] Misra, S., Chopra, K., Sinha, V. & Medhi, B. Galantamine-loaded solid–lipid nanoparticles for enhanced brain delivery: preparation, characterization, in vitro and in vivo evaluations. Drug Deliv. 23, 1434–1443 (2016). source

      Not checked in the free run.

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    Premisecitation

    DNA encoding IL-10 and IL-4 encapsulated in polymeric nanoparticles delivered into white blood cells inhibits T cell response against residual native islet cells in prediabetic animal model, inhibiting diabetes development in 75% of animals.

    “DNA encoding interleukin (IL)-10 and IL-4 encapsulated in polymeric nanoparticles has been delivered into white blood cells to inhibit the T cell response against residual native islet cells in a prediabetic animal model. It was found to be very helpful in diabetic management because it inhibited diabetes development in 75% of the animals.94”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] Ko, K. S., Lee, M., Koh, J. J. & Kim, S. W. Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. Mol. Ther. 4, 313–316 (2001). source

      Not checked in the free run.

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    Premisecitation

    Encapsulation of curcumin and NGF in combination led to synergistic effect and showed clinical application in mitigating Aβ-induced neurotoxicity.

    “Interestingly, the encapsulation of curcumin and NGF in combination led to a synergistic effect and showed a clinical application in mitigating Aβ-induced neurotoxicity.109,110”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [109] Kuo, Y.-c & Lin, C.-C. Rescuing apoptotic neurons in Alzheimer’s disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin. Int. J. Nanomed. 10, 2653 (2015). source

      Not checked in the free run.

    • cites [110] Kuo, Y.-C. & Chou, P.-R. Neuroprotection against degeneration of SK-N-MC cells using neuron growth factor-encapsulated liposomes with surface cereport and transferrin. J. Pharm. Sci. 103, 2484–2497 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    RT-loaded chitosan NPs improved memory function with reduced toxicity in a mouse model.

    “Furthermore, RT-loaded chitosan NPs also improved memory function with reduced toxicity in a mouse model.102”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] Nagpal, K., Singh, S. & Mishra, D. Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety. Int. J. Biol. Macromol. 59, 72–83 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SLNs loaded with galantamine hydrobromide demonstrated enhanced bioavailability (two times higher than pure drug) and improved memory and cognition in animals.

    “Interestingly, SLNs loaded with galantamine hydrobromide demonstrated enhanced bioavailability (two times higher than that of the pure drug) and improved memory and cognition in animals.104”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [104] Misra, S., Chopra, K., Sinha, V. & Medhi, B. Galantamine-loaded solid–lipid nanoparticles for enhanced brain delivery: preparation, characterization, in vitro and in vivo evaluations. Drug Deliv. 23, 1434–1443 (2016). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Memantine is a promising drug molecule that inhibits excess glutamate activity, important for memory and learning.

    “Memantine (a glutamate receptor antagonist) is a promising drug molecule that inhibits excess glutamate activity, which is important for memory and learning.99”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [99] Molinuevo, J. L., Lladó, A. & Rami, L. Memantine: targeting glutamate excitotoxicity in Alzheimer’s disease and other dementias. Am. J. Alzheimer’s. Dis. Other Demen. 20, 77–85 (2005). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NGF adsorbed on PBCA-80-coated poly(butylcyanoacrylate) reversed scopolamine-induced amnesia and slowed progression of neurodegeneration in a rat model.

    “NGF adsorbed on PBCA-80-coated poly(butylcyanoacrylate) reversed scopolamine-induced amnesia and slowed the progression of neurodegeneration in a rat model.108”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Kurakhmaeva, K. B. et al. Brain targeting of nerve growth factor using poly (butyl cyanoacrylate) nanoparticles. J. Drug Target. 17, 564–574 (2009). source

      Not checked in the free run.

    • Rests on an assumption: Nerve growth factor does not cross the blood–brain barrier efficiently.

  • May combine two claims.

    Interpretationown data

    Presence of CSK peptide increases bioavailability of insulin-loaded nanoparticles at targeted site, resulting in effective depression of blood glucose level.

    “Hence, the presence of CSK peptide increases the bioavailability of the insulin-loaded nanoparticles at the targeted site, which results in effective depression of the blood glucose level.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Jin, Y. et al. Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport. Biomaterials 33, 1573–1582 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Maximum DA entrapment efficiency was 63%, and DA peak was highest at day 3 in CSF and plasma of rats while maintaining adequate level up to 30 days compared to inherent DA levels.

    “The maximum DA entrapment efficiency was 63%, and the DA peak was reported to be highest at day 3 in both the cerebrospinal fluid and plasma of rats while maintaining an adequate level up to 30 days compared to inherent DA levels.117”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [117] Pillay, S. et al. Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain. Int. J. Pharm. 382, 277–290 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neural stem cells of subventricular zone treated with miR-124 NPs showed significant proliferation of neuroblasts but lower number of proliferating glial cells or astrocyte-like cells than control.

    “Neural stem cells of the subventricular zone treated with microRNA miR-124 NPs showed significant proliferation of neuroblasts (Ki67+/DCX+) but a lower number of proliferating glial cells or astrocyte-like cells (Ki67+/GFAP+) than in the control.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [132] Saraiva, C., Paiva, J., Santos, T., Ferreira, L. & Bernardino, L. MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson’s disease. J. Control. Release 235, 291–305 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Polymeric nanoparticles containing perfluoro-1,5-crown ether mediated miR-124 delivery and increased number of migrating neuroblasts in healthy mice and 6-OHDA mouse models for PD.

    “Polymeric nanoparticles containing perfluoro-1,5-crown ether mediated miR-124 delivery and increased the number of migrating neuroblasts both in healthy mice and in 6-OHDA mouse models for PD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [132] Saraiva, C., Paiva, J., Santos, T., Ferreira, L. & Bernardino, L. MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson’s disease. J. Control. Release 235, 291–305 (2016). source

      Not checked in the free run.

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    Premisecitation

    Intrastriatal implantation of silica-DA nanoformulation reversed symptoms in hemiparkinsonian rats with no observable side effects.

    “Intrastriatal implantation of silica-DA nanoformulation also reversed the symptoms in hemiparkinsonian rats with no observable side effects.118”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] López, T. et al. Treatment of Parkinson’s disease: nanostructured sol–gel silica–dopamine reservoirs for controlled drug release in the central nervous system. Int. J. Nanomed. 6, 19 (2011). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PLGA-MS-mediated GDNF release demonstrated antiparkinsonian effects, confirmed by improvement in amphetamine-induced rotational behavior test.

    “Similar results were also observed by Garbayo et al., where PLGA-MS-mediated GDNF release demonstrated antiparkinsonian effects, as confirmed by the improvement in the amphetamine-induced rotational behavior test.130”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [130] Garbayo, E. et al. Effective GDNF brain delivery using microspheres—a promising strategy for Parkinson’s disease. J. Controlled Release 135, 119–126 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PLGA/collagen MS may be used to deliver GDNF, and in vitro application stimulates differentiation of neuronal progenitor cells into mature neurons.

    “Gujral et al. also showed that PLGA/collagen MS may be used to deliver GDNF, and in vitro application suggests that it stimulates the differentiation of neuronal progenitor cells into mature neurons.131”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [131] Gujral, C., Minagawa, Y., Fujimoto, K., Kitano, H. & Nakaji-Hirabayashi, T. Biodegradable microparticles for strictly regulating the release of neurotrophic factors. J. Control. Release 168, 307–316 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DA-loaded chitosan NPs facilitate transport across the blood-brain barrier and minimize cytotoxicity.

    “DA-loaded chitosan NPs facilitate transport across the BBB and minimize the cytotoxicity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [116] Trapani, A. et al. Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery. Int. J. Pharm. 419, 296–307 (2011). source

      Not checked in the free run.

    • Rests on an assumption: Limited permeability across the blood–brain barrier restricts the therapeutic potential of dopaminergic molecules in Parkinson's disease.

  • May combine two claims.

    Premisecitation

    GDNF-loaded microsphere increased TH-positive fibers in striatum and substantia nigra, suggesting neuroprotection and neurorestoration activity.

    “Apart from this GDNF-loaded microsphere increase in TH-positive fibers in the striatum and substantia nigra, the results suggested neuroprotection and neurorestoration activity.129,130”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [129] Jollivet, C. et al. Long-term effect of intra-striatal glial cell line-derived neurotrophic factor-releasing microspheres in a partial rat model of Parkinson’s disease. Neurosci. Lett. 356, 207–210 (2004). source

      Not checked in the free run.

    • cites [130] Garbayo, E. et al. Effective GDNF brain delivery using microspheres—a promising strategy for Parkinson’s disease. J. Controlled Release 135, 119–126 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Decreased expression of SOX-9 and Jagged1 was observed after miR-124 NPs, which promotes neurogenesis by modulating other signaling pathways.

    “Furthermore, decreased expression of SOX-9 and Jagged1 was observed, which promotes neurogenesis by modulating other signaling pathways (Fig. 4c, d).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [132] Saraiva, C., Paiva, J., Santos, T., Ferreira, L. & Bernardino, L. MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson’s disease. J. Control. Release 235, 291–305 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Nanomaterials avoid rapid renal excretion and remain in circulation for extended durations, facilitating extravasation and accumulation in desired tissue.

    “Importantly, nanomaterials avoid rapid renal excretion and remain in circulation for extended durations. This characteristic feature facilitates extravasation through the vascular system and allows nanomaterials to accumulate and distribute well in the desired tissue or organs, thereby achieving maximum therapeutic efficacy at minimum drug dosage.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Chronic administration of rotigotine-loaded PLGA-MS in monkey and SD rats showed sustained release behavior accompanied by better safety.

    “Other investigators also confirmed that chronic administration of rotigotine-loaded PLGA-MS in monkey and SD rats showed sustained release behavior accompanied by better safety.123,124”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [123] Ye, L. et al. Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in SD rats. Food Chem. Toxicol. 56, 81–92 (2013). source

      Not checked in the free run.

    • cites [124] Tian, J. et al. Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in Cynomolgus monkeys. Food Chem. Toxicol. 52, 143–152 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sustained delivery and higher bioavailability of ropirinole, bromocriptine and apomorphine could be achieved through SLNs.

    “Sustained delivery and higher bioavailability of ropirinole, bromocriptine and apomorphine could be achieved through SLNs.126,127”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [126] Pardeshi, C. V., Rajput, P. V., Belgamwar, V. S., Tekade, A. R. & Surana, S. J. Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach. Drug Deliv. 20, 47–56 (2013). source

      Not checked in the free run.

    • cites [127] Tsai, M.-J. et al. Oral apomorphine delivery from solid lipid nanoparticles with different monostearate emulsifiers: pharmacokinetic and behavioral evaluations. J. Pharm. Sci. 100, 547–557 (2011). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Levodopa/benserazide encapsulated in PLGA-NPs significantly reduced dyskinesis and improved PD symptoms and associated biochemical markers in PD animal model.

    “Similarly, a significant reduction in dyskinesis and improvement in PD symptoms and associated biochemical markers (ΔfosB, c-AMP-regulated phosphoprotein or phosphorylated dopamine) were observed in the PD animal model after the administration of levodopa/benserazide encapsulated in PLGA-NPs.120,121”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [120] Ren, T. et al. Sustained-release formulation of levodopa methyl ester/benserazide for prolonged suppressing dyskinesia expression in 6-OHDA-leisoned rats. Neurosci. Lett. 502, 117–122 (2011). source

      Not checked in the free run.

    • cites [121] Yang, X. et al. Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats. Int. J. Nanomed. 7, 2077 (2012).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PLA magnetic NPs of aliskiren showed better bioavailability and better control of BP.

    “PLA magnetic NPs of aliskiren showed better bioavailability and eventually better control of BP.142”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [142] Antal, I. et al. Magnetic poly (D, L-lactide) nanoparticles loaded with aliskiren: a promising tool for hypertension treatment. J. Magn. Magn. Mater. 380, 280–284 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Polymer-based nisoldipine eudragit S100 nanoparticles released drug at pH of colon, circumventing gut and liver metabolism and extending systemic availability.

    “Polymer-based nisoldipine eudragit S100 nanoparticles released the drug from the polymer at the pH of the colon, which could circumvent drug metabolism in the gut and liver, thereby maintaining the integrity of the drug and extending the availability in systemic circulation.139”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [139] Nepolean, R., Narayanan, N., Subramaniyan, N., Venkateswaran, K. & Vinoth, J. Colon targeted methacrylic acid copolymeric nanoparticles for improved oral bioavailability of nisoldipine. Int. J. Biol. Pharm. Res. 3, 962–967 (2012).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    N1177 showed approximately 100-fold higher resolution than conventional CT scans and is being clinically tested in human subjects.

    “Approximately 100-fold higher resolution than conventional computed tomography scans showed promise, and this approach is being clinically tested for application in human subjects.152”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [152] Weissleder, R., Nahrendorf, M. & Pittet, M. J. Imaging macrophages with nanoparticles. Nat. Mater. 13, 125 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Liposomal encapsulation of lercanidipine improved drug absorption and bioavailability and reduced BP.

    “Similarly, liposomal encapsulation of lercanidipine resulted in significantly improved drug absorption and bioavailability and eventually marked reduction in BP.147”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [147] Deshpande, P. B. et al. A novel nanoproliposomes of lercanidipine: Development, in vitro and preclinical studies to support its effectiveness in hypertension therapy. Life Sci. 162, 125–137 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    M12PEG mitigated lipid accumulation, inflammation, and neointimal hyperplasia in atherosclerotic disease.

    “M12PEG was also able to mitigate lipid accumulation (Oil Red O), inflammation (COX-2) and neointimal hyperplasia (smooth muscle cell, α-actin), demonstrating its efficacy in atherosclerotic disease (Fig. 5e–g).154”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [154] Lewis, D. R. et al. Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo. Proc. Natl Acad. Sci. USA 112, 2693–2698 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Successful entrapment of anti-hypertensive drugs by nanoparticulate system protects drug in circulation and prolongs systemic availability at desired concentration, regulating BP.

    “Briefly, the successful entrapment of anti-hypertensive drugs by the nanoparticulate system protects the drug in circulation and prolongs the systemic availability of drugs at the desired concentration, which eventually regulates the BP.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    siRNA is highly prone to degradation and requires delivery vehicle to circumvent degradation by endo- and exonucleases.

    “As such, siRNA is highly prone to degradation and requires a delivery vehicle to circumvent degradation by endo- and exonucleases present in the blood circulation and cells.150”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [150] Nolte, A., Schneider, M., Walker, T. & Wendel, H. in Regenerative Medicine and Tissue Engineering-Cells and Biomaterials (IntechOpen, 2011).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inhalable montelukast-loaded nanostructured lipid carriers improved systemic bioavailability (12-fold) and therapeutic outcomes compared to montelukast aqueous solutions.

    “Inhalable montelukast-loaded nanostructured lipid carriers have been found to improve systemic bioavailability (12-fold) and eventual therapeutic outcomes compared to those of montelukast aqueous solutions.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [173] Patil-Gadhe, A., Kyadarkunte, A., Patole, M. & Pokharkar, V. Montelukast-loaded nanostructured lipid carriers: part II pulmonary drug delivery and in vitro–in vivo aerosol performance. Eur. J. Pharm. Biopharm. 88, 169–177 (2014). source

      Not checked in the free run.

    • cites [174] Patil-Gadhe, A. & Pokharkar, V. Montelukast-loaded nanostructured lipid carriers: part I oral bioavailability improvement. Eur. J. Pharm. Biopharm. 88, 160–168 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nanosized chitosan-coated PLGA NPs sustain release of CaMKIIN with effective cellular uptake.

    “Nanosized chitosan-coated PLGA NPs were reported to have the ability to sustain the release of CaMKIIN with effective cellular uptake (Fig. 7a–c).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [175] Morris, A. S. et al. Cationic CaMKII inhibiting nanoparticles prevent allergic asthma. Mol. Pharm. 14, 2166–2175 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inhalable drugs reduce dosing frequency, and bypassing first pass hepatic metabolism reduces hepatocellular toxicity.

    “Inhalable drugs reduce dosing frequency, and bypassing the first pass hepatic metabolism reduces hepatocellular toxicity.173,174”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [173] Patil-Gadhe, A., Kyadarkunte, A., Patole, M. & Pokharkar, V. Montelukast-loaded nanostructured lipid carriers: part II pulmonary drug delivery and in vitro–in vivo aerosol performance. Eur. J. Pharm. Biopharm. 88, 169–177 (2014). source

      Not checked in the free run.

    • cites [174] Patil-Gadhe, A. & Pokharkar, V. Montelukast-loaded nanostructured lipid carriers: part I oral bioavailability improvement. Eur. J. Pharm. Biopharm. 88, 160–168 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ONO-1301 NPs significantly improved myocardial blood flow and decreased infarct area.

    “Myocardial blood flow was significantly improved, accompanied by a significant decrease in infarct area (Fig. 6b, c).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [162] Yajima, S. et al. Prostacyclin analogue–loaded nanoparticles attenuate myocardial Ischemia/reperfusion Injury in rats. JACC: Basic Transl. Sci. 4, 318–331 (2019).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ONO-1301 NPs upregulated pro-angiogenic cytokines in ischemic myocardium, preserving vascular network and facilitating myocardial blood flow.

    “Furthermore, upregulated pro-angiogenic cytokines (e.g., vascular endothelial growth factor and angiopoietin-1) were reported in the ischemic myocardium, which preserves the dense vascular network and facilitates myocardial blood flow.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [162] Yajima, S. et al. Prostacyclin analogue–loaded nanoparticles attenuate myocardial Ischemia/reperfusion Injury in rats. JACC: Basic Transl. Sci. 4, 318–331 (2019).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CCR2 siRNA treatment reduced monocyte number in atherosclerotic plaques and reduced infarct size after coronary artery occlusion.

    “Moreover, treatment reduced their number in atherosclerotic plaques and reduced the infarct size after coronary artery occlusion.158”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [158] Leuschner, F. et al. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat. Biotechnol. 29, 1005 (2011). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ONO-1301 NPs downregulated troponin I and inflammatory cytokines IL-1β, IL-6 and TNF-α, leading to enhanced myocardial blood flow and reduced infarct size.

    “ONO-1301 NPs helped downregulate troponin I (Fig. 6d) along with the inflammatory cytokines IL-1β, IL-6 and tumor necrosis factor-α, which eventually led to enhanced myocardial blood flow and reduced infarct size.162”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [162] Yajima, S. et al. Prostacyclin analogue–loaded nanoparticles attenuate myocardial Ischemia/reperfusion Injury in rats. JACC: Basic Transl. Sci. 4, 318–331 (2019).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Telodendrimer has higher loading capacity, higher stability and slower release of drug formulations than other types.

    “Telodendrimer is a class of nanocarrier that has been reported to have higher loading capacity, higher stability and slower release of drug formulations than other types.176”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [176] Jackson, J. K., Zhang, X., Llewellen, S., Hunter, W. L. & Burt, H. M. The characterization of novel polymeric paste formulations for intratumoral delivery. Int. J. Pharm. 270, 185–198 (2004). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chitosan-coated NPs specifically localize in lungs and fluoresce up to 48 h, suggesting release of CaMKIIN with higher bioavailability and high retention time.

    “These chitosan-coated NPs specifically localize in the lungs and fluoresce up to 48 h, which suggests that NPs are able to release CaMKIIN with higher bioavailability and high retention time (Fig. 7e, f).175”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [175] Morris, A. S. et al. Cationic CaMKII inhibiting nanoparticles prevent allergic asthma. Mol. Pharm. 14, 2166–2175 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PLGA and PLA are promising FDA-approved drug delivery carriers and are currently used in clinical settings.

    “Among polymeric nanoparticles, PLGA and poly-lactic acid (PLA) are promising FDA-approved drug delivery carriers and are currently being used in clinical settings.156”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [156] Tyler, B., Gullotti, D., Mangraviti, A., Utsuki, T. & Brem, H. Polylactic acid (PLA) controlled delivery carriers for biomedical applications. Adv. Drug Deliv. Rev. 107, 163–175 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NPs facilitate drug delivery directly to target tissues, improving lung deposition and therapeutic effects of anti-asthmatic drugs while attenuating adverse side effects.

    “NPs facilitate drug delivery directly to the target tissues, thus improving the lung deposition and eventually the therapeutic effects of anti-asthmatic drugs while attenuating the adverse side effects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [168] SILVA, A. L. et al. Nanoparticle-based therapy for respiratory diseases. An. da Academia Brasileira de. Ciências 85, 137–146 (2013). source

      Not checked in the free run.

    • Rests on an assumption: Inhalation minimizes drug resistance, therapeutic dose, and side effects when delivering nanomedicines to the lung.

  • May combine two claims.

    Premisecitation

    Polymeric nanomaterials entrap drug efficiently and allow sustained release or stimuli-responsive release.

    “Polymeric nanomaterials entrap the drug efficiently and either allow drug release in a sustained manner or facilitate the release kinetics in response to cellular or extracellular stimuli, such as temperature, pH, and redox potential.164”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [164] Liechty, W. B., Kryscio, D. R., Slaughter, B. V. & Peppas, N. A. Polymers for drug delivery systems. Annu. Rev. Chem. biomolecular Eng. 1, 149–173 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Biodegradable DNA NPs have shown potential for inhaled lung gene therapy, capable of overcoming mucus barrier of lung airways.

    “In recent times, biodegradable DNA NPs have shown potential for inhaled lung gene therapy, which is capable of overcoming the mucus barrier of lung airways.183”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [183] Mastorakos, P. et al. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc. Natl Acad. Sci. USA 112, 8720–8725 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ciprofloxacin encapsulated in liposomes has been employed in anti-TB therapy, offering pulmonary delivery through nebulization.

    “Ciprofloxacin encapsulated in liposomes has been employed in anti-TB therapy, offering pulmonary delivery through nebulization.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [207] Finlay, W. & Wong, J. Regional lung deposition of nebulized liposome-encapsulated ciprofloxacin. Int. J. pharmaceutics 167, 121–127 (1998). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The majority of macrophages incubated with RITC-labeled NP-RIF internalized the fluorescent nanoparticles and exhibited 10-fold higher fluorescence intensity than untreated control macrophages.

    “The majority of the macrophages that were incubated with RITC-labeled NP-RIF internalized the fluorescent nanoparticles and exhibited 10-fold higher fluorescence intensity than the untreated control macrophages.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [204] Clemens, D. L. et al. Targeted intracellular delivery of antituberculosis drugs to Mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles. Antimicrobial Agents Chemother. 56, 2535–2545 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The inhalation route is advantageous for pulmonary delivery of anti-TB drugs and requires lower doses to achieve therapeutic effects.

    “In this context, the inhalation route is advantageous for the pulmonary delivery of anti-TB drugs and requires lower doses to achieve therapeutic effects. The pulmonary delivery of drugs is a convenient and effective approach for the treatment of TB.202”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [202] Willis, L., Hayes, D. & Mansour, H. M. Therapeutic liposomal dry powder inhalation aerosols for targeted lung delivery. Lung 190, 251–262 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Nasal delivery of anti-TB drugs directly to lungs achieves pharmacologically effective drug concentrations in AMs, ensuring better treatment outcomes.

    “This approach has the advantage of achieving pharmacologically effective drug concentrations in the AMs, which ensures better treatment outcomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Drug-specific surface functionalization has been employed for rifampicin, and further functionalization with poly(ethylene imine) yields high loading and controlled drug delivery to MTB-infected macrophages compared to uncoated MSNP.

    “Drug-specific surface functionalization has been employed for RIF, and further functionalization with poly(ethylene imine) (PEI) yields high loading and controlled drug delivery to MTB-infected macrophages compared to uncoated MSNP.204”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [204] Clemens, D. L. et al. Targeted intracellular delivery of antituberculosis drugs to Mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles. Antimicrobial Agents Chemother. 56, 2535–2545 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Current COPD treatment with inhaled corticosteroids, anticholinergics, and β2-agonists controls symptoms but does not cure underlying disease.

    “The current treatment strategy for COPD includes inhaled corticosteroids, anticholinergics, and β2-agonists, which have been primarily effective in controlling the symptoms but do not cure the underlying disease.184”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [184] Vogelmeier, C. F. et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am. J. Respir. Crit. Care Med. 195, 557–582 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nanodrug delivery system reduces adverse systemic side effects and frequency of drug administration, leading to better patient compliance.

    “Furthermore, the nanodrug delivery system reduces the adverse systemic side effects and frequency of drug administration, which eventually leads to better patient compliance.196,197”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [196] Pham, D.-D., Fattal, E. & Tsapis, N. Pulmonary drug delivery systems for tuberculosis treatment. Int. J. pharmaceutics 478, 517–529 (2015). source

      Not checked in the free run.

    • cites [197] Andrade, F. et al. Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases. Adv. drug Deliv. Rev. 65, 1816–1827 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Delamanid and bedaquiline have shown promise to fight against MDR TB.

    “Delamanid and bedaquiline have shown promise to fight against multidrug resistance (MDR) TB.200”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [200] Tadolini, M. et al. First case of extensively drug-resistant tuberculosis treated with both delamanid and bedaquiline. Eur. Respiratory J. 48, 935–938 (2016). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MTB can multiply and spread to other organs, resulting in extrapulmonary TB.

    “Therefore, MTB can multiply and spread to other organs of the body, resulting in extrapulmonary TB.195”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [195] Krishnan, N., Robertson, B. D. & Thwaites, G. The mechanisms and consequences of the extra-pulmonary dissemination of Mycobacterium tuberculosis. Tuberculosis 90, 361–366 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Finlay et al. showed high loading efficiency (90%) of liposomes made of phosphatidylcholine and cholesterol, of which up to 30% remained encapsulated after nebulization.

    “Finlay et al. showed high loading efficiency (90%) of liposomes made of phosphatidylcholine (PC) and Chol, of which up to 30% remained encapsulated after nebulization.207”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [207] Finlay, W. & Wong, J. Regional lung deposition of nebulized liposome-encapsulated ciprofloxacin. Int. J. pharmaceutics 167, 121–127 (1998). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PEGylated immunoconjugated PLGA-nanoparticles demonstrated targeted delivery of ibuprofen to neutrophils, inhibiting neutrophilic inflammation in LPS-induced murine model of obstructive lung disease.

    “A formulation of PEGylated immunoconjugated PLGA-nanoparticles demonstrated the targeted delivery of ibuprofen (an anti-inflammatory drug) to neutrophils, which inhibited neutrophilic inflammation in a lipopolysaccharide-induced murine model of obstructive lung disease.190”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [190] Vij, N., Min, T., Bodas, M., Gorde, A. & Roy, I. Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases. Nanomed.: Nanotechnol., Biol. Med. 12, 2415–2427 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    In the enhanced permeation and retention effect, leaky vasculature promotes permeation of small molecules and poor lymphatic drainage allows retention and accumulation of chemotherapeutics in the tumor.

    “Several methods have been proposed for targeting tumors, e.g., the enhanced permeation and retention effect where the leaky vasculature promotes the permeation of small molecules and poor lymphatic drainage allows the retention and accumulation of chemotherapeutics in the tumor.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Common features of tumors include leaky vasculature and poor lymphatic drainage.

  • May combine two claims.

    Premisecitation

    All these formulations showed sustained release for up to 72 h with an initial burst drug release pattern of less than 20% in the first 6 h.

    “Interestingly, all these formulations showed sustained release for up to 72 h with an initial burst drug release pattern of less than 20% in the first 6 h.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [217] Pandey, R. & Khuller, G. Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis. Tuberculosis 85, 227–234 (2005). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    RIF encapsulated in liposomes made of PC and cholesterol as aerosols showed a sustained release profile with an encapsulation efficiency of ~30%.

    “In another study, RIF encapsulated in liposomes (made of PC and Chol) as aerosols showed a sustained release profile with an encapsulation efficiency of ~30%.210”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [210] Gaur, P. K. et al. Targeted drug delivery of Rifampicin to the lungs: formulation, characterization, and stability studies of preformed aerosolized liposome and in situ formed aerosolized liposome. Drug Dev. Ind. Pharm. 36, 638–646 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Liposomes 90 nm in diameter could escape from leaky tumor vasculature but did not permeate away from the tumor for a week.

    “In one of the reports, liposomes 90 nm in diameter could escape from the leaky tumor vasculature but did not permeate away from the tumor for a week.227”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [227] Yuan, F. et al. Mirovascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res. 54, 3352–3356 (1994).

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Smaller molecules accumulate in tumors faster than larger molecules, but larger molecules can be retained for longer times within the tumor.

    “Smaller molecules accumulate in tumors faster than larger molecules, but larger molecules can be retained for longer times within the tumor.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In vivo studies confirmed higher accumulation of rifabutin in lungs with less immunogenicity for mannose-coated formulations.

    “Furthermore, in vivo studies confirmed the higher accumulation of rifabutin in lungs with less immunogenicity for mannose-coated formulations.216”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [216] Nimje, N. et al. Mannosylated nanoparticulate carriers of rifabutin for alveolar targeting. J. Drug Target. 17, 777–787 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This approach reduces systemic and local toxicity and provides better results than uncoated formulations.

    “This approach reduces systemic and local toxicity and provides better results than uncoated formulations.212”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [212] Deol, P., Khuller, G. & Joshi, K. Therapeutic efficacies of isoniazid and rifampin encapsulated in lung-specific stealth liposomes against Mycobacterium tuberculosis infection induced in mice. Antimicrobial Agents Chemother. 41, 1211–1214 (1997). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DPPC has been employed for INH delivery, but the loading efficiency was lower (~37%).

    “DPPC has also been employed for INH delivery; however, the loading efficiency was found to be lower (~37%).209”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] Chimote, G. & Banerjee, R. Evaluation of antitubercular drug‐loaded surfactants as inhalable drug‐delivery systems for pulmonary tuberculosis. J. Biomed. Mater. Res. A. 89, 281–292 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    In the enhanced permeation effect, the delivered agent is released locally and rapidly taken up by cancerous cells to accomplish its function.

    “In the enhanced permeation effect (EPR), the delivered agent is released locally and rapidly taken up by cancerous cells to accomplish its function.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A mannose coating on solid lipid nanoparticles made of tristearin is suitable for drug delivery, and cellular uptake of rifabutin was enhanced up to six-fold compared to uncoated formulations.

    “A mannose coating on SLNs made of tristearin has been found to be suitable for drug delivery, and the cellular uptake of rifabutin was enhanced up to six-fold compared to that of uncoated formulations.216”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [216] Nimje, N. et al. Mannosylated nanoparticulate carriers of rifabutin for alveolar targeting. J. Drug Target. 17, 777–787 (2009). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Mannose is a common ligand associated with lipid nanoparticles.

    “Mannose is a common ligand associated with lipid NPs.214”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [214] Yu, W., Liu, C., Liu, Y., Zhang, N. & Xu, W. Mannan-modified solid lipid nanoparticles for targeted gene delivery to alveolar macrophages. Pharm. Res. 27, 1584–1596 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The rifampicin-loaded freeze-dried liposome formulation was optimized with a drug entrapment efficiency of 79%, and a sustained release pattern could be achieved showing higher anti-TB activity than that of the pure drug.

    “This formulation was optimized with a drug entrapment efficiency of 79%, and a sustained release pattern could be achieved showing higher anti-TB activity than that of the pure drug.211”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [211] Patil, J. S., Devi, V. K., Devi, K. & Sarasija, S. A novel approach for lung delivery of rifampicin-loaded liposomes in dry powder form for the treatment of tuberculosis. Lung India. 32, 331 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The main advantage of local therapy is that the pharmaceutical concentration of chemotherapeutics in the tumor environment can be maximized, and toxicity to other nontargeted organs can be minimized.

    “The main advantage of local therapy is that the pharmaceutical concentration of chemotherapeutics in the tumor environment can be maximized, and the toxicity to other nontargeted organs can be minimized.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [219] Chew, S. A. & Danti, S. Biomaterial-Based Implantable Devices for Cancer Therapy. Adv. Healthc. Mater. 6, 1600766 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The DPPC/INH formulation was biocompatible, and sustained release was maintained for up to 24 h with a burst release of 50% in the first 5 h.

    “However, the formulation was biocompatible, and sustained release was maintained for up to 24 h with a burst release of 50% in the first 5 h.209”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [209] Chimote, G. & Banerjee, R. Evaluation of antitubercular drug‐loaded surfactants as inhalable drug‐delivery systems for pulmonary tuberculosis. J. Biomed. Mater. Res. A. 89, 281–292 (2009). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several classes of materials have been developed for targeted therapy, including biodegradable polymers, liposomes, dendrimers, nanoshells and nucleic acid-based nanoparticles.

    “Several classes of materials have been developed to date for targeted therapy, including biodegradable polymers, liposomes, dendrimers, nanoshells and nucleic acid-based NPs.2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Singh, N. K. et al. Nanostructure controlled anti-cancer drug delivery using poly (ε-caprolactone) based nanohybrids. J. Mater. Chem. 22, 17853–17863 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Rifapentine-loaded proliposomal dry powder was effective in direct delivery of the drug to the lungs and eventually had a better therapeutic effect.

    “Similarly, rifapentine-loaded proliposomal dry powder was effective in the direct delivery of the drug to the lungs and eventually had a better therapeutic effect.211”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [211] Patil, J. S., Devi, V. K., Devi, K. & Sarasija, S. A novel approach for lung delivery of rifampicin-loaded liposomes in dry powder form for the treatment of tuberculosis. Lung India. 32, 331 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Polyurethane-grafted chitosan-based brush hydrogels have been used as injectable hydrogels in tissue engineering.

    “Polyurethane-grafted chitosan-based brush hydrogels have been used as injectable hydrogels in tissue engineering.251”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [251] Mahanta, A. K., Senapati, S. & Maiti, P. A polyurethane–chitosan brush as an injectable hydrogel for controlled drug delivery and tissue engineering. Polym. Chem. 8, 6233–6249 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Coupling of hydrophilic terminal groups with folate units for active targeting showed high stability and exhibited sustained release.

    “The coupling of hydrophilic terminal groups with folate units for active targeting showed high stability and exhibited sustained release.247”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [247] Shi, C. et al. Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles. Biomaterials 35, 8711–8722 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Conjugation of cholesterol altered particle size and enhanced encapsulation efficiency.

    “The conjugation of cholesterol altered the particle size and enhanced the encapsulation efficiency.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [248] Kumari, P. et al. Cholesterol-conjugated poly(D, L-lactide)-based micelles as a nanocarrier system for effective delivery of curcumin in cancer therapy. Drug Deliv. 24, 209–223 (2017). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Targeted therapy is the combination of targeted delivery with sustained drug release, which allows maximum utilization of the drug delivered at the tumor site.

    “Targeted therapy is thus the combination of targeted delivery with sustained drug release, which allows the maximum utilization of the drug delivered at the tumor site.236”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [236] Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5, 161 (2005). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Polymeric nanoparticles can be formulated for encapsulation of various hydrophilic and hydrophobic smaller molecules, particularly drugs and macromolecules such as proteins or peptides.

    “Polymeric nanoparticles can be formulated for the encapsulation of various hydrophilic and hydrophobic smaller molecules, particularly drugs and macromolecules such as proteins or peptides.232”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [232] Perez, C. et al. Poly (lactic acid)-poly (ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA. J. Control. Release 75, 211–224 (2001). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sustained release of paclitaxel and curcumin occurred in sequential kinetics, and curcumin downregulated nuclear factor NF-kB and enhanced the therapeutic efficacy of paclitaxel.

    “The sustained release of paclitaxel and curcumin occurred in sequential kinetics, and curcumin downregulated nuclear factor NF-kB and enhanced the therapeutic efficacy of paclitaxel.239”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [239] Ruttala, H. B. & Ko, Y. T. Liposomal co-delivery of curcumin and albumin/paclitaxel nanoparticle for enhanced synergistic antitumor efficacy. Colloids Surf. B: Biointerfaces 128, 419–426 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    pH-sensitive nanoparticles composed of dendrimer building blocks showed better tumor penetration and dissociated into smaller sizes in the tumor environment.

    “Li and coworkers showed the size effect of pH-sensitive nanoparticles composed of dendrimer building blocks with better tumor penetration and their dissociation into smaller sizes in the tumor environment.245”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [245] Li, H.-J. et al. Smart superstructures with ultrahigh pH-sensitivity for targeting acidic tumor microenvironment: instantaneous size switching and improved tumor penetration. ACS nano 10, 6753–6761 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Drug release from layered double hydroxide formulations was controlled, and higher cytotoxicity was observed in HeLa cells, further confirmed through in vivo tumor suppression in a murine model, indicating its application as a drug delivery vehicle.

    “The drug release was controlled, and higher cytotoxicity was observed in HeLa cells, which was further confirmed through in vivo tumor suppression in a murine model, indicating its application as a drug delivery vehicle.1,231”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Senapati, S. et al. Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions. J. Control. Release 224, 186–198 (2016). source

      Not checked in the free run.

    • cites [231] Senapati, S. et al. Engineered cellular uptake and controlled drug delivery using two dimensional nanoparticle and polymer for cancer treatment. Mol. Pharm. 15, 679–694 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The rate of drug release can be governed through polymer modification, the development of new polymers, or the synthesis of copolymers.

    “The rate of release can be governed through polymer modification, the development of new polymers, or the synthesis of copolymers.233–235”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [233] Langer, R. New methods of drug delivery. Science 249, 1527–1533 (1990). source

      Not checked in the free run.

    • cites [234] Langer, R. Drug delivery and targeting. Nature, 392, 5–10 (1998). source

      Not checked in the free run.

    • cites [235] Langer, R. & Folkman, J. Polymers for the sustained release of proteins and other macromolecules. Nature 263, 797 (1976). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Dendrimers are one of the important classes of drug carriers and operate by encapsulating drugs in their unique macromolecular architecture.

    “Dendrimers are one of the important classes of drug carriers and operate by encapsulating drugs in their unique macromolecular architecture.242”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [242] Andresen, T. L., Jensen, S. S. & Jørgensen, K. Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release. Prog. lipid Res. 44, 68–97 (2005). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Liposomes are amphiphilic in nature and are composed of natural or synthetic lipids.

    “Liposomes are amphiphilic in nature and are composed of natural or synthetic lipids.237”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [237] Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 4, 145 (2005). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Highly porous, 3D-interconnected nanohybrid scaffolds/hydrogels controlled drug release and were biocompatible.

    “Highly porous, 3D-interconnected nanohybrid scaffolds/hydrogels controlled drug release and were biocompatible as well.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [252] Mahanta, A. K. et al. Nanoparticle-induced controlled drug delivery using chitosan-based hydrogel and scaffold: application to bone regeneration. Mol. Pharm. 16, 327–338 (2018). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Encapsulation of drugs in micelles is achieved through various physical, chemical or electrostatic interactions.

    “The encapsulation of drugs in micelles is achieved through various physical, chemical or electrostatic interactions.246”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [246] Park, J. H. et al. Polymeric nanomedicine for cancer therapy. Prog. Polym. Sci. 33, 113–137 (2008). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Layered double hydroxides have drawn attention for potential as a drug carrier due to high drug-loading capacity, biocompatibility, and anion exchange capability.

    “A well-known type of 2D nanocarrier, layered double hydroxides, has drawn attention for its potential as a drug carrier due to its high drug-loading capacity, biocompatibility, and anion exchange capability.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Internal and external surfaces of layered double hydroxides can easily be modified for incorporation of targeting ligands, and their high specific surface areas make them advantageous for diverse applications.

    “The internal and external surfaces of layered double hydroxides (LDHs) can easily be modified for the incorporation of targeting ligands, and their high specific surface areas make them advantageous for diverse applications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The scaffold was found to be safe and very effective in bone regeneration compared to pure chitosan.

    “The scaffold has been found to be safe and very effective in bone regeneration compared to pure chitosan.252”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [252] Mahanta, A. K. et al. Nanoparticle-induced controlled drug delivery using chitosan-based hydrogel and scaffold: application to bone regeneration. Mol. Pharm. 16, 327–338 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The main benefits of biodegradable polymers are maintaining drug concentration in the optimum range for a longer period of time and thereby increasing drug efficacy and improving patient compliance.

    “The main benefits of these biodegradable polymers are maintaining the drug concentration in the optimum range for a longer period of time and thereby increasing the efficacy of the drug and improving patient compliance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Liposomal formulations with anticancer drugs have been approved by the FDA for human use.

    “Liposomal formulations with anticancer drugs have been approved by the FDA for human use.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Microgels loaded with DOX showed anticancer activity against HeLa cells, and supramolecular hydrogels of α CD- and polyethylene-modified gold nanocrystals exhibited sustained drug release via host-guest interaction.

    “Microgels loaded with DOX showed anticancer activity against HeLa cells, and supramolecular hydrogels of α CD- and polyethylene-modified gold nanocrystals exhibited sustained drug release via host-guest interaction.253”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [253] Yu, J., Ha, W., Sun, J.-n & Shi, Y.-p Supramolecular hybrid hydrogel based on host–guest interaction and its application in drug delivery. ACS Appl. Mater. Interfaces 6, 19544–19551 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Injectable gel of the CD superstructure, when placed subcutaneously in melanoma mice, showed complete shrinkage, a greater effect than that of the pure drug, and none of the side effects observed in conventional chemotherapy occurred.

    “Injectable gel of this superstructure, when placed subcutaneously in melanoma mice, showed complete shrinkage, which has a greater effect than that of the pure drug, and none of the side effects observed in conventional chemotherapy occurred.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [256] Shukla, A., Singh, A. P., Dubey, T., Hemalatha, S. & Maiti, P. Third Generation Cyclodextrin Graft with Polyurethane Embedded in Hydrogel for a Sustained Drug Release: Complete Shrinkage of Melanoma. ACS Appl. Bio Mater. 2, 1762–1771 (2019). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    Although most preclinical studies have been reported to be successful, clinical translation is a major challenge that requires a large number of well-defined clinical trials in various disease cohorts.

    “Although most of the preclinical studies have been reported to be successful, clinical translation is a major challenge that requires a large number of well-defined clinical trials in various disease cohorts.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Nanoencapsulation increases the circulation half-lives and drug retention in the body.

    “Since nanoencapsulation increases the circulation half-lives and drug retention in the body, short-term and long-term side effects must be assessed before its authorized application in human diseases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    A suitable drug carrier is important to ensure site-specific sustained drug delivery.

    “A suitable drug carrier is important to ensure site-specific sustained drug delivery.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The biodistribution study showed that the drug was retained for a longer time from Mod-Gel-d while it was rapidly eliminated in the pure form.

    “The biodistribution study of the pure drug and gel showed the efficacy of sustained release, since the drug is retained for a longer time period from Mod-Gel-d while it is rapidly eliminated in the pure form as a drug (Fig. 8h).256”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [256] Shukla, A., Singh, A. P., Dubey, T., Hemalatha, S. & Maiti, P. Third Generation Cyclodextrin Graft with Polyurethane Embedded in Hydrogel for a Sustained Drug Release: Complete Shrinkage of Melanoma. ACS Appl. Bio Mater. 2, 1762–1771 (2019). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Nanotechnology-based diagnosis and treatment strategies have been successfully delivered in both preclinical and clinical trials.

    “Nanotechnology-based diagnosis and treatment strategies have been successfully delivered in both preclinical and clinical trials.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Thermosensitive HDI-PF127/HA hydrogel possessed adequate physiochemical and biological properties and was used as a delivery carrier for sustained release of anticancer drugs in cancer therapy.

    “This thermosensitive HDI-PF127/HA hydrogel possessed adequate physiochemical and biological properties and was used as a delivery carrier for the sustained release of anticancer drugs in cancer therapy.254”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [254] Chen, Y.-Y., Wu, H.-C., Sun, J.-S., Dong, G.-C. & Wang, T.-W. Injectable and thermoresponsive self-assembled nanocomposite hydrogel for long-term anticancer drug delivery. Langmuir 29, 3721–3729 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Complete melanoma shrinkage with higher biodistribution of the drug through a gel placed subcutaneously is an effective carrier for cancer treatment.

    “Therefore, complete melanoma shrinkage with higher biodistribution of the drug through a gel placed subcutaneously is an effective carrier for cancer treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Treatment of mice bearing melanoma with developed patches of drug-loaded graft copolymers showed significant tumor suppression compared to the pure drug, where slight suppression was noticed arising from burst release.

    “Treatment of mice bearing melanoma with developed patches of drug-loaded graft copolymers showed significant tumor suppression compared to the effect of the pure drug, where slight suppression was noticed arising from its burst release.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [255] Shukla, A. et al. Efficacy of polyurethane graft on cyclodextrin to control drug release for tumor treatment. J. colloid Interface Sci. 534, 215–227 (2019). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Drugs embedded in nanoparticles, whether inorganic or organic, exhibit sustained drug release and thereby exhibit much greater therapeutic effects than the pure drug.

    “However, drugs embedded in nanoparticles, whether inorganic or organic, exhibit sustained drug release and thereby exhibit much greater therapeutic effects than the pure drug.”
    Quote in the paperSubstantial claim
113 of 113

  • The paper relies on this without support.

    The inability or limited ability of currently available drug molecules to cross the blood–brain barrier is the major reason for their limited therapeutic effects in neurodegenerative diseases.

    “The inability or limited ability to cross the blood–brain barrier (BBB) is the major reason for the limited therapeutic effects of the currently available drug molecules.”

  • The paper relies on this without support.

    Nerve growth factor does not cross the blood–brain barrier efficiently.

    “Nerve growth factor (NGF) does not cross the BBB efficiently”

  • The paper relies on this without support.

    Limited permeability across the blood–brain barrier restricts the therapeutic potential of dopaminergic molecules in Parkinson's disease.

    “However, limited permeability across the BBB restricts the therapeutic potential of these dopaminergic molecules.”

  • The paper relies on this without support.

    Chronic administration of levodopa induces dyskinesis.

    “The chronic administration of levodopa induces dyskinesis”

  • The paper relies on this without support.

    Pulsatile administration of the dopaminergic system promotes motor complications such as dyskinesia.

    “pulsatile administration promotes motor complications (dyskinesia)”

  • The paper relies on this without support.

    pH differences of the gastrointestinal tract hinder the pharmacological activity of drugs.

    “the pH differences of gastrointestinal tracts (acidic in stomach and basic in the intestine) hinder the pharmacological activity of the drugs.”

  • The paper relies on this without support.

    The major reason for the failure of most clinical trials in myocardial ischemia-reperfusion injury is insufficient drug delivery within a limited therapeutic time window.

    “The major reason for the failure of most clinical trials in myocardial IR injury is insufficient drug delivery within a limited therapeutic time window.”

  • The paper relies on this without support.

    Inhalation minimizes drug resistance, therapeutic dose, and side effects when delivering nanomedicines to the lung.

    “inhalation is an advantageous approach to deliver nanomedicines to the lung because this delivery method minimizes drug resistance, therapeutic dose, and side effects.”

  • The paper relies on this without support.

    CaMKII is overexpressed in asthmatic patients.

    “Reports suggest the overexpression of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in asthmatic patients.”

  • The paper relies on this without support.

    CaMKII inhibition reduces disease phenotypes of allergic asthma.

    “CaMKII inhibition reduced disease phenotypes of allergic asthma”

  • The paper relies on this without support.

    The major challenges in nanotherapeutics of COPD are airway defense, mucus hypersecretion and severe inflammation.

    “The major challenges in the nanotherapeutics of COPD are airway defense, mucus hypersecretion and severe inflammation.”

  • The paper relies on this without support.

    New drugs are always needed to fight drug-resistant tuberculosis.

    “new drugs are always needed to fight drug-resistant TB.”

  • The paper relies on this without support.

    Repeated administration of high doses is required to achieve therapeutic levels of anti-TB drugs by the oral route due to rapid hepatic first-pass metabolism and reduced gastro-intestinal absorption.

    “Although the oral route is the most convenient and least expensive, repeated administration of high doses is required to achieve therapeutic levels of anti-TB drugs due to rapid hepatic first-pass metabolism and reduced gastro-intestinal absorption.”

  • The paper relies on this without support.

    Encapsulation of drugs into nano drug delivery systems offers potential benefits to penetrate and cross biological barriers to reach targeted sites in the lungs.

    “In this context, the encapsulation of drugs into nano drug delivery systems offers a number of potential benefits to penetrate and cross the biological barriers to reach the targeted sites in the lungs.”

  • The paper relies on this without support.

    Technologies such as chemotherapy, injections of micro/nanoparticles, immunotherapy, and radiation therapy possess defects associated with systemic delivery, such as poor/low drug concentration at the tumor site, nonselectivity towards cells or tissues leading to toxicity, and low efficacy due to short half-life.

    “However, these technologies possess some defects associated with systemic delivery, such as poor/low drug concentration at the tumor site, nonselectivity towards cells or tissues leading to toxicity, and the low efficacy of the drugs due their short half-life.”

  • The paper relies on this without support.

    Common features of tumors include leaky vasculature and poor lymphatic drainage.

    “Common features of tumors include leaky vasculature and poor lymphatic drainage.”

  • The paper relies on this without support.

    In conventional chemotherapy, it is difficult to achieve therapeutic concentrations at the tumor site through systemic delivery.

    “In conventional chemotherapy, it is difficult to achieve therapeutic concentrations at the tumor site through systemic delivery.”

  • The paper relies on this without support.

    The physicochemical properties of drugs encapsulated in nanoparticles are the most important characteristic for achieving proper drug distribution in the lungs.

    “The physicochemical properties of drugs encapsulated in nanoparticles are the most important characteristic for achieving a proper drug distribution in lungs.”
18 of 18

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Dendrimers consist of an inner layer and an outer layer; functional groups for drug conjugation and targeting make up the outer layer; drug encapsulation efficiency, drug toxicity, and controlled release mechanisms are improved in the inner layer.

    “They consist of an inner layer and an outer layer. Functional groups that are used for drug conjugation and targeting make up the outer layer. The drug encapsulation efficiency, drug toxicity, and controlled release mechanisms are all improved in the inner layer.26”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [25]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Levodopa treatment is assigned to both AD and PD

    Minor

    The Parkinson's disease section says levodopa therapy is used in AD patients, whereas the paper earlier identifies levodopa as a treatment prescribed for PD patients.

  • Figure 3 panels cited for memory results depict other outcomes

    Minor

    The text cites panels 3d and 3e as support for improved spatial learning and memory, but the caption identifies them as a drug-release plot and a schematic, respectively.

2 of 2

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 3

  1. Maiti, P., Senapati, S. & Saraf, S. Inhibition of Chronic Osteomyelitis using Sustained Release of Drug from Biodegradable Polymeric Chip. Clin. Oncol. 3, 1406 (2018).
  2. Nepolean, R., Narayanan, N., Subramaniyan, N., Venkateswaran, K. & Vinoth, J. Colon targeted methacrylic acid copolymeric nanoparticles for improved oral bioavailability of nisoldipine. Int. J. Biol. Pharm. Res. 3, 962–967 (2012).
  3. Sia, I. G. & Wieland, M. L. in Mayo Clinic Proceedings. 348–361 (Elsevier).

Cited by

Sorted by citations

Related

Authors
Singh, A. P., Biswas, A., Shukla, A., & Maiti, P.
Affiliations
Indian Institute of Technology BHU (IN)
Corresponding author
Maiti, Pralay
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2019-08-30
Volume
4
Issue
1
Pages
33-33
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-019-0068-3
PMC
PMC6799838
OpenAlex
W2970857608
Semantic Scholar
aefca7d18121ad24e99711b4c465dc6fbf0de8cc
Cited by
645
References
262
Citations by year
2026: 53 · 2025: 105 · 2024: 123 · 2023: 98 · 2022: 96 · 2021: 89 · 2020: 76 · 2019: 5
FWCI
4.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Science and Engineering Research Board (PDF/2016/004063)
  • Biotechnology Industry Research Assistance Council
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Pharmacology and Nanomedicine Research
Keywords
nanomedicine, targeted drug delivery, drug carriers, chronic disease, liposomes, nanoparticles, hydrogels, micelles, dendrimers, mesoporous particles, diabetes mellitus, cancer, atherosclerosis, myocardial ischemia, asthma, pulmonary tuberculosis, Parkinson's disease, Alzheimer's disease, gene therapy, nucleic acid delivery, peptide delivery, biocompatible nanomaterials

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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