Nanotechnology approaches for global infectious diseases

In the paper

“a recent study used spontaneous nanoliposome antigen particleization to show efficacy of a multistage, multi-antigen vaccine in mice and rabbits 116 .”

What the sources say

• Partly supported

  The Antigen multiplexing section reports that a multistage, multi-antigen SNAP vaccine induced antibodies in mice that recognized the expected parasite life stages. The Antigen particleization section and Rabbit immunization methods report rabbit results for Pfs25 alone, not for the multi-antigen vaccine. The claim therefore overstates what was shown in rabbits. (LLM, conf=0.88)

  cites [116] Huang, W.-C. et al. A malaria vaccine adjuvant based on recombinant antigen binding to liposomes. Nat. Nanotechnol. https://doi.org/10.1038/s41565-018-0271-3 (2018). sourceExperimental — accuracy not yet measured

In the paper

“HIV-infected individuals require lifelong treatment to ensure control of the viral burden 10 .”

What the sources say

• Not checked yetcites [10] Kirtane, A. R., Langer, R. & Traverso, G. Past, present, and future drug delivery systems for antiretrovirals. J. Pharm. Sci. 105, 3471–3482 (2016). source

In the paper

“Unfortunately, clinical trials for these infectious diseases (IDs) are also lagging compared with conditions such as cancer and cardiovascular diseases (Fig. 1d) 1”

What the sources say

• Not checked yetcites [1] Roth, G. A. et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease Study 2017. Lancet 392, 1736–1788 (2018). source

In the paper

“To treat TB, a combination of pills must be consumed over a period of several months to years-often multiple times a day 11 .”

What the sources say

• Not checked yetcites [11] Treatment of Tuberculosis: Guidelines 4th edn (WHO, 2010); https://www.who.int/tb/publications/2010/9789241547833/en/

In the paper

“The lack of safe and effective drugs is central to our inability to treat IDs 2 .”

What the sources say

• Not checked yetcites [2] Kinch, M. S., Patridge, E., Plummer, M. & Hoyer, D. An analysis of FDA-approved drugs for infectious disease: antibacterial agents. Drug Discov. Today 19, 1283–1287 (2014). source

In the paper

“Prolonged and complicated dosing regimens with high pill burden result in lower patient adherence and, ultimately, failure of treatment.”

In the paper

“Dwindling amounts of drug released during the terminal phase of the release period may lead to a 'long pharmacologic tail' 20 , a period of slowly declining drug levels.”

What the sources say

• Not checked yetcites [20] Landovitz, R. J., Kofron, R. & McCauley, M. The promise and pitfalls of long-acting injectable agents for HIV prevention. Curr. Opin. HIV AIDS 11, 122–128 (2016). source

In the paper

“Following subcutaneous or intramuscular injection, drug absorption into systemic circulation is dictated by the rate of dissolution of the drug crystals in the interstitial fluid 16 .”

What the sources say

• Not checked yetcites [16] Trezza, C., Ford, S. L., Spreen, W., Pan, R. & Piscitelli, S. Formulation and pharmacology of long-acting cabotegravir. Curr. Opin. HIV AIDS 10, 239–245 (2015). source

In the paper

“Compared with systemic administration, local delivery to the site of infection is likely to enhance on-target (and minimize off-target) drug exposure.”

In the paper

“Leakage out of the vaginal tract was highest for uncoated nanoparticles (~13% of the dose within 0.5 h).”

What the sources say

• Not checked yetcites [23] Cu, Y., Booth, C. J. & Saltzman, W. M. In vivo distribution of surface-modified PLGA nanoparticles following intravaginal delivery. J. Control. Release 156, 258–264 (2011). source

In the paper

“Improved tissue uptake of PEGylated nanoparticles may be attributed to their higher diffusivity through the mucous layer-an observation shown using multiple particle tracking experiments by the Hanes lab 24 .”

What the sources say

• Not checked yetcites [24] Lai, S. K. et al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl Acad. Sci. USA 104, 1482–1487 (2007). source

In the paper

“Second, in rodent models, drug concentrations become undetectable at about 24 h post-dose, suggesting that sustained delivery may be possible for only a relatively short time.”

In the paper

“Several barriers impede complete coverage of the vaginal tract and prolonged residence of the drug delivery system 21 .”

What the sources say

• Not checked yetcites [21] das Neves, J., Nunes, R., Machado, A. & Sarmento, B. Polymer-based nanocarriers for vaginal drug delivery. Adv. Drug Deliv. Rev. 92, 53–70 (2015). source

In the paper

“Despite early positive results in clinical trials for urinary tract infections and Mycobacterium infections 15 , development of the formulation was discontinued in 2000.”

What the sources say

• Not checked yetcites [15] Schiffelers, R., Storm, G. & Bakker-Woudenberg, I. Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies. J. Antimicrob. Chemother. 48, 333–344 (2001). source

In the paper

“Finally, encapsulation in nanocarriers may protect labile drugs (such as nucleic acids) in harsh physiological conditions such as low pH or the presence of enzymes.”

In the paper

“However, the improved tissue concentrations were observed only within the first hour of administration, and not at later times.”

What the sources say

• Not checked yetcites [25] Cunha-Reis, C. et al. Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. J. Control. Release 243, 43–53 (2016). source

In the paper

“In murine skin infection models of S. aureus and methicillin-resistant S. aureus biofilms, nitric oxide-releasing nanoparticles decreased overall wound bacterial burden compared with both unloaded nanoparticles and the control group 39 .”

What the sources say

• Not checked yetcites [39] Martinez, L. R. et al. Antimicrobial and healing efficacy of sustained release nitric oxide nanoparticles against Staphylococcus aureus skin infection. J. Invest. Dermatol. 129, 2463–2469 (2009). source

In the paper

“These benefits cannot be attributed completely to nanoformulation as changing the route of administration from oral to pulmonary is likely to contribute heavily to this improvement.”

In the paper

“Administering the antiretroviral azidothymidine in poly(hexacyanoacrylate) nanoparticles improved its accumulation in reticuloendothelial system (RES) organs such as the liver, lungs and spleen 44 .”

What the sources say

• Not checked yetcites [44] Löbenberg, R., Araujo, L., von Briesen, H., Rodgers, E. & Kreuter, J. Body distribution of azidothymidine bound to hexyl-cyanoacrylate nanoparticles after i.v. injection to rats. J. Control. Release 50, 21–30 (1998). source

In the paper

“In mouse studies, pulmonary delivery of amorphous itraconazole nanoparticles resulted in a tenfold higher drug concentration in the lungs compared with oral administration of its commercial formulation (Sporanox) and the unformulated drug 31 .”

What the sources say

• Not checked yetcites [31] Vaughn, J. M. et al. Single dose and multiple dose studies of itraconazole nanoparticles. Eur. J. Pharm. Biopharm. 63, 95–102 (2006). source

In the paper

“The half-life of the liposome-encapsulated drug in mouse lungs was about double that of the free drug (~3 h versus ~1.5 h).”

What the sources say

• Not checked yetcites [33] Wong, J. P. et al. Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection. J. Control. Release 92, 265–273 (2003). source

In the paper

“In comparison with the free drug, the nanoparticle-encapsulated quorum sensing inhibitor showed better in vitro control of virulence as measured by quantifying levels of a bacterial product (pyocyanin).”

What the sources say

• Not checked yetcites [34] Nafee, N. et al. Antibiotic-free nanotherapeutics: ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors. J. Control. Release 192, 131–140 (2014). source

In the paper

“In a mouse model of lethal HSV-2 infection, intravaginal administration of oligofectamine-complexed small interfering RNA (siRNA) targeting genes encoding viral envelope and DNA binding proteins resulted in improved survival compared with untreated controls 27 .”

What the sources say

• Not checked yetcites [27] Palliser, D. et al. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 439, 89–94 (2006). source

In the paper

“Interestingly, a study found that 60% of clinical samples from chronic infection sites contained biofilms compared with 6% found in acute infections 38 .”

What the sources say

• Not checked yetcites [38] James, G. A. et al. Biofilms in chronic wounds. Wound Repair Regen. 16, 37–44 (2008). source

In the paper

“N -acetyl cysteine enhanced the diffusivity of DNA-loaded poly(lysine) polyplexes in the sputum of cystic fibrosis patients by more than fivefold 36 .”

What the sources say

• Not checked yetcites [36] Suk, J. S. et al. N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles. Mol. Ther. 19, 1981–1989 (2011). source

In the paper

“However, formulations that cannot penetrate mucous layers and biofilms have low pulmonary bioavailability due to rapid enzymatic deactivation, sequestration and elimination by coughing 22,29 .”

What the sources say

• Not checked yetcites [22] Leal, J., Smyth, H. D. C. & Ghosh, D. Physicochemical properties of mucus and their impact on transmucosal drug delivery. Int. J. Pharm. 532, 555–572 (2017). source
• Not checked yetcites [29] Roy, I. & Vij, N. Nanodelivery in airway diseases: challenges and therapeutic applications. Nanomedicine 6, 237–244 (2010). source

In the paper

“Confocal microscopy also demonstrated that polysorbate 80-coated nanoparticles diffused across porcine mucous.”

What the sources say

• Not checked yetcites [34] Nafee, N. et al. Antibiotic-free nanotherapeutics: ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors. J. Control. Release 192, 131–140 (2014). source

In the paper

“In a murine Aspergillus fumigatus infection model, the same group observed an increased median survival in the pulmonary nanoparticle treated group (7.5 days) compared with oral Sporanox treated group (5 days) 32 .”

What the sources say

• Not checked yetcites [32] Alvarez, C. A. et al. Aerosolized nanostructured itraconazole as prophylaxis against invasive pulmonary aspergillosis. J. Infect. 55, 68–74 (2007). source

In the paper

“Improved on-target accumulation occurs because of enhanced nanocarrier permeability at sites of infection compared with uninfected tissue.”

In the paper

“Furthermore, they found that nanoparticles were able to decrease Pseudomonas aeruginosa biofilm formation by > 70% compared with untreated controls 35 .”

What the sources say

• Not checked yetcites [35] Duong, H. T. T. et al. Nanoparticle (star polymer) delivery of nitric oxide effectively negates Pseudomonas aeruginosa biofilm formation. Biomacromolecules 15, 2583–2589 (2014). source

In the paper

“Hence, strategies that enhance intracellular accumulation of drugs and targeting to subcellular locations may improve efficacy.”

In the paper

“due to the non-specific biodistribution of nanocarriers that typically precedes triggering, drug release at non-target sites cannot be avoided.”

In the paper

“Local injection of anti-protein A-functionalized nanoparticles was observed to be nearly twice as effective at killing S. aureus in murine cutaneous infection models compared with the control 57 .”

What the sources say

• Not checked yetcites [57] Kim, M.-H. et al. Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus infection. Ann. Biomed. Eng. 41, 598–609 (2013). source

In the paper

“A common limitation of these studies is that comparison of the stimuli-sensitive nanoparticles with non-degradable nanoparticles was not performed.”

In the paper

“There have also been several studies that show higher accumulation of nanocarriers at sites of infection compared with non-infected sites (reviewed in ref. 47 ).”

What the sources say

• Not checked yetcites [47] Laverman et al. Liposomes for scintigraphic detection of infection and inflammation. Adv. Drug Deliv. Rev. 37, 225–235 (1999). source

In the paper

“Although nanoencapsulation may enhance drug accumulation at sites of infection, there are certain limitations when translating from rodent models to humans.”

In the paper

“Binding of the antibody-functionalized nanoparticles to cultures of S. aureus was quantified by flow cytometry and demonstrated a 2.5-fold increase in binding compared with the IgG-coated nanoparticles.”

What the sources say

• Not checked yetcites [57] Kim, M.-H. et al. Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus infection. Ann. Biomed. Eng. 41, 598–609 (2013). source

In the paper

“In one study 48 , there was an ~40-fold greater liposome concentration (per cent injected dose per gram of tissue) in the abscess compared with the muscle.”

What the sources say

• Not checked yetcites [48] Laverman, P. et al. Microscopic localization of PEG-liposomes in a rat model of focal infection. J. Control. Release 75, 347–355 (2001). source

In the paper

“The change in vascular permeability and drug targeting depended, in part, on the infectious agent.”

In the paper

“Mannose-functionalized liposomes showed a 1.5-fold higher exposure in alveolar macrophages compared with unmodified liposomes.”

What the sources say

• Not checked yetcites [54] Chono, S., Tanino, T., Seki, T. & Morimoto, K. Efficient drug targeting to rat alveolar macrophages by pulmonary administration of ciprofloxacin incorporated into mannosylated liposomes for treatment of respiratory intracellular parasitic infections. J. Control. Release 127, 50–58 (2008). source

In the paper

“In a mouse model of pulmonary P. aeruginosa infection, treatment with targeted nanoparticles improved survival over the free-drug control by nearly 50 percentage points.”

What the sources say

• Not checked yetcites [62] Zhang, C. Y., Gao, J. & Wang, Z. Bioresponsive nanoparticles targeted to infectious microenvironments for sepsis management. Adv. Mater. 30, 1803618 (2018). source

In the paper

“The benefit of PEG coating was reduced at low infection severity.”

What the sources say

• Not checked yetcites [51] Bakker-Woudenberg, I. A. et al. Liposomes with prolonged blood circulation and selective localization in Klebsiella pneumoniae-infected lung tissue. J. Infect. Dis. 168, 164–171 (1993). source

In the paper

“Importantly, in rats that had the most severe lung infection, PEG-coated liposomes (half-life = 27 h) resulted in approximately fourfold higher concentrations compared with uncoated liposomes (half-life = 19 h) 51 .”

What the sources say

• Not checked yetcites [51] Bakker-Woudenberg, I. A. et al. Liposomes with prolonged blood circulation and selective localization in Klebsiella pneumoniae-infected lung tissue. J. Infect. Dis. 168, 164–171 (1993). source

In the paper

“some studies show that the degree of targeting is directly correlated with the severity of infection 51,52 .”

What the sources say

• Not checked yetcites [51] Bakker-Woudenberg, I. A. et al. Liposomes with prolonged blood circulation and selective localization in Klebsiella pneumoniae-infected lung tissue. J. Infect. Dis. 168, 164–171 (1993). source
• Not checked yetcites [52] Bakker-Woudenberg, I. A., Lokerse, A. F., ten Kate, M. T. & Storm, G. Enhanced localization of liposomes with prolonged blood circulation time in infected lung tissue. Biochim. Biophys. Acta 1138, 318–326 (1992). source

In the paper

“Poor drug diffusion across the host cell membrane and its active efflux via drug transporters can reduce activity against intracellular pathogens 63 .”

What the sources say

• Not checked yetcites [63] Carryn, S. et al. Intracellular pharmacodynamics of antibiotics. Infect. Dis. Clin. North Am. 17, 615–634 (2003). source

In the paper

“In a zebrafish model of methicillin-resistant S. aureus infection, the phosphatase-sensitive nanoparticles enhanced survival by 20 percentage points over free-drug controls.”

What the sources say

• Not checked yetcites [60] Xiong, M.-H. et al. Bacteria-responsive multifunctional nanogel for targeted antibiotic delivery. Adv. Mater. 24, 6175–6180 (2012). source

In the paper

“In an in vitro model of recombinant S. typhirium infection, gentamicin-loaded pH-sensitive liposomes showed threefold higher activity than the free drug.”

What the sources say

• Not checked yetcites [65] Lutwyche, P. et al. Intracellular delivery and antibacterial activity of gentamicin encapsulated in pH-sensitive liposomes. Antimicrob. Agents Chemother. 42, 2511–2520 (1998). source

In the paper

“In a 20 day efficacy study, 100% of the mice administered the peptide-functionalized nanoparticles survived, compared with roughly 40% survival in the non-functionalized-nanoparticle and free-vancomycin cohorts.”

What the sources say

• Not checked yetcites [56] Hussain, S. et al. Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy. Nat. Biomed. Eng. 2, 95–103 (2018). source

In the paper

“In comparison with the free drug, the targeted liposomes showed a 23-fold higher bioavailability in the alveolar macrophages.”

What the sources say

• Not checked yetcites [54] Chono, S., Tanino, T., Seki, T. & Morimoto, K. Efficient drug targeting to rat alveolar macrophages by pulmonary administration of ciprofloxacin incorporated into mannosylated liposomes for treatment of respiratory intracellular parasitic infections. J. Control. Release 127, 50–58 (2008). source

In the paper

“at an acidic pH, the plug is lost, resulting in drug release.”

What the sources say

• Not checked yetcites [66] Clemens, D. L. et al. Targeted Intracellular delivery of antituberculosis drugs to Mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles. Antimicrob. Agents Chemother. 56, 2535–2545 (2012). source

In the paper

“Confocal microscopy showed that only pH-sensitive liposomes released the marker intracellularly in murine macrophages.”

What the sources say

• Not checked yetcites [65] Lutwyche, P. et al. Intracellular delivery and antibacterial activity of gentamicin encapsulated in pH-sensitive liposomes. Antimicrob. Agents Chemother. 42, 2511–2520 (1998). source

In the paper

“initial work done by Langer and Folkman 70 , which showed that macromolecules such as proteins could be encapsulated in small polymer-based carriers”

What the sources say

• Not checked yetcites [70] Langer, R. & Folkman, J. Polymers for the sustained release of proteins and other macromolecules. Nature 263, 797–800 (1976). source

In the paper

“Despite higher cell uptake of pH-insensitive liposomes, they showed inferior activity to the pH-sensitive formulation.”

What the sources say

• Not checked yetcites [65] Lutwyche, P. et al. Intracellular delivery and antibacterial activity of gentamicin encapsulated in pH-sensitive liposomes. Antimicrob. Agents Chemother. 42, 2511–2520 (1998). source

In the paper

“Marker release was abrogated by bafilomycin, an inhibitor of endosome acidification.”

What the sources say

• Not checked yetcites [65] Lutwyche, P. et al. Intracellular delivery and antibacterial activity of gentamicin encapsulated in pH-sensitive liposomes. Antimicrob. Agents Chemother. 42, 2511–2520 (1998). source

In the paper

“The evolution of antibiotic-degrading enzymes is a major mechanism causing bacterial resistance.”

What the sources say

• Not checked yetcites [3] Munita, J. M. & Arias, C. A. Mechanisms of antibiotic resistance. Microbiol. Spectrum 4, VMBF-0016-2015. (2016). source

In the paper

“Peptide-based antigen assembled into nanoparticles have also been developed for vaccination against SARS-CoV-2 78 .”

What the sources say

• Not checked yetcites [78] Tian, J.-H. et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat. Commun. 12, 372 (2021). source

In the paper

“Couvreur and colleagues showed that poly(cyanoacrylate) nanoparticles colocalized with S. typhirium in phagosomes of macrophages, resulting in enhanced intracellular targeting of ampicillin 79 .”

What the sources say

• Not checked yetcites [79] Pinto-Alphandary, H. et al. Intracellular visualization of ampicillin-loaded nanoparticles in peritoneal macrophages infected in vitro with Salmonella typhimurium. Pharm. Res. 11, 38–46 (1994). source

In the paper

“Liposomes have also been used for protecting drugs against bacterial enzymes 83 .”

What the sources say

• Not checked yetcites [83] Nacucchio, M. C., Bellora, M. J., Sordelli, D. O. & D’Aquino, M. Enhanced liposome-mediated activity of piperacillin against staphylococci. Antimicrob. Agents Chemother. 27, 137–139 (1985). source

In the paper

“They also allow drugs to be administered to dysphagic patients, for example individuals infected with HIV and suffering from opportunistic oesophageal infections 88 .”

What the sources say

• Not checked yetcites [88] Swindells, S., Flexner, C., Fletcher, C. V. & Jacobson, J. M. The critical need for alternative antiretroviral formulations, and obstacles to their development. J. Infect. Dis. 204, 669–674 (2011). source

In the paper

“Multiple antimicrobial agents can be packaged within the same nanoparticle to increase the likelihood of overcoming existing drug resistance mechanisms instead of using one drug alone (Fig. 4e).”

In the paper

“Local disruption of the biofilms increased the permeability and therefore susceptibility to the antibiotic tobramycin.”

What the sources say

• Not checked yetcites [81] Teirlinck, E. et al. Laser-induced vapour nanobubbles improve drug diffusion and efficiency in bacterial biofilms. Nat. Commun. 9, 4518 (2018). source

In the paper

“Toti et al. found that PLGA nanoparticles loaded with a fluorescent dye accumulated with chlamydial inclusion bodies in infected human lung epithelial cells 80 .”

What the sources say

• Not checked yetcites [80] Toti, U. S. et al. Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles. Biomaterials 32, 6606–6613 (2011). source

In the paper

“Teirlinck et al. showed that laser irradiation of gold nanoparticles resulted in the formation of nanobubbles that disrupted this diffusional barrier 81 .”

What the sources say

• Not checked yetcites [81] Teirlinck, E. et al. Laser-induced vapour nanobubbles improve drug diffusion and efficiency in bacterial biofilms. Nat. Commun. 9, 4518 (2018). source

In the paper

“Shaaban et al. developed poly(caprolactone) nanoparticles loaded with imipenem 82 and found that drug-loaded nanoparticles conferred 250- and 62.5-fold decreases in minimal inhibitory concentrations compared with free imipenem in in vitro cultures of imipenem-resistant K. pneumoniae and P. aeruginosa , respectively.”

What the sources say

• Not checked yetcites [82] Shaaban, M. I., Shaker, M. A. & Mady, F. M. Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates. J. Nanobiotechnol. 15, 29 (2017). source

In the paper

“Specifically, nanoparticles of two antiretrovirals, cabotegravir and rilpivirine, are being actively pursued in the clinic.”

What the sources say

• Not checked yetcites [16] Trezza, C., Ford, S. L., Spreen, W., Pan, R. & Piscitelli, S. Formulation and pharmacology of long-acting cabotegravir. Curr. Opin. HIV AIDS 10, 239–245 (2015). source
• Not checked yetcites [17] Williams, P. E., Crauwels, H. M. & Basstanie, E. D. Formulation and pharmacology of long-acting rilpivirine. Curr. Opin. HIV AIDS 10, 233–238 (2015). source

In the paper

“Cabotegravir 16 and rilpivirine 17 were chosen owing to their efficacy at low oral doses and low water solubility.”

What the sources say

• Not checked yetcites [16] Trezza, C., Ford, S. L., Spreen, W., Pan, R. & Piscitelli, S. Formulation and pharmacology of long-acting cabotegravir. Curr. Opin. HIV AIDS 10, 239–245 (2015). source
• Not checked yetcites [17] Williams, P. E., Crauwels, H. M. & Basstanie, E. D. Formulation and pharmacology of long-acting rilpivirine. Curr. Opin. HIV AIDS 10, 233–238 (2015). source

In the paper

“When co-administered with exogenous β -lactamase, piperacillin-loaded liposomes provided twofold growth inhibition compared with the free drug co-administered with β -lactamase.”

What the sources say

• Not checked yetcites [83] Nacucchio, M. C., Bellora, M. J., Sordelli, D. O. & D’Aquino, M. Enhanced liposome-mediated activity of piperacillin against staphylococci. Antimicrob. Agents Chemother. 27, 137–139 (1985). source

In the paper

“we have developed an orally administered gastric retentive dosage form that can reduce dosing frequency from daily to weekly 98 .”

What the sources say

• Not checked yetcites [98] Kirtane, A. R. et al. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nat. Commun. 9, 2 (2018). source

In the paper

“In contrast, half-lives of rilpivirine and cabotegravir in tablets have been estimated to be ~1-2 days (refs. 91,92 ).”

What the sources say

• Not checked yetcites [91] Verloes, R. et al. Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long-acting formulation in healthy volunteers. HIV Med. 16, 477–484 (2015). source
• Not checked yetcites [92] Ford, S. L. et al. Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Antimicrob. Agents Chemother. 57, 5472–5477 (2013). source

In the paper

“In Phase IIb clinical trials, the combination of rilpivirine and cabotegravir nanosuspensions enabled disease suppression equivalent to oral tablets of cabotegravir and abcavir-lamivudine 93 .”

What the sources say

• Not checked yetcites [93] Margolis, D. A. et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Lancet Infect. Dis. 15, 1145–1155 (2015). source

In the paper

“Covalent attachment of heparin and monoclonal antibodies to liposomes has been proven to selectively target infected RBCs in vitro 105,108 .”

What the sources say

• Not checked yetcites [105] Marques, J. et al. Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery. Nanomedicine13, 515–525 (2017). source
• Not checked yetcites [108] Urbán, P., Estelrich, J., Cortés, A. & Fernàndez-Busquets, X. A nanovector with complete discrimination for targeted delivery to Plasmodium falciparum-infected versus non-infected red blood cells in vitro. J. Control. Release 151, 202–211 (2011). source

In the paper

“due to the low uptake of artemisinin in parasite-infected red blood cells (RBCs), these drugs provide only symptomatic relief at low doses 103 .”

What the sources say

• Not checked yetcites [103] Fidock, D. A. Priming the antimalarial pipeline. Nature 465, 297–298 (2010). source

In the paper

“An alternative approach was recently tested in mice and involves injecting a solution of the drug and polymer in an organic solvent subcutaneously 97 . A surgically removable drug depot (~0.75 cm diameter in mice) forms as the organic solvent diffuses out of the injection site.”

What the sources say

• Not checked yetcites [97] Kovarova, M. et al. Nanoformulations of rilpivirine for topical pericoital and systemic coitus-independent administration efficiently prevent HIV transmission. PLoS Pathog. 11, e1005075 (2015). source

In the paper

“Nanotechnology can also improve the oral bioavailability of poorly water-soluble antimalarials, such artemether and tafenoquine.”

In the paper

“The combination therapy exhibited promising antimalarial efficacy in vivo against a resistant parasite strain 113 .”

What the sources say

• Not checked yetcites [113] Kumar, S., Singh, R. K., Sharma, R., Murthy, R. S. R. & Bhardwaj, T. R. Design, synthesis and evaluation of antimalarial potential of polyphosphazene linked combination therapy of primaquine and dihydroartemisinin. Eur. J. Pharm. Sci. 66, 123–137 (2015). source

In the paper

“Efavirenz and lopinavir nanoparticles made using this strategy are currently awaiting clinical testing (NCT02631473).”

What the sources say

• Not checked yetcites NCT02631473

In the paper

“In rats, the optimized nanoparticle formulation was bioequivalent to lopinavir dissolved in alcohol and propylene glycol 99 .”

What the sources say

• Not checked yetcites [99] Giardiello, M. et al. Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies. Nat. Commun. 7, 13184 (2016). source

In the paper

“unstable in gastric acid”

What the sources say

• Not checked yetcites [120] Jain, R. et al. in Handbook of Nanomaterials for Industrial Applications Ch. 33 (Elsevier, 2018).

In the paper

“In the lungs and spleen of infected mice, no tubercle bacilli could be detected after five oral doses of drug-loaded solid lipid nanoparticles administered every tenth day, whereas 46 daily doses of oral free drugs were required to achieve the same therapeutic benefit 123 .”

What the sources say

• Not checked yetcites [123] Pandey, R., Sharma, S. & Khuller, G. K. Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis 85, 415–420 (2005). source

In the paper

“These examples highlight the promise of pulmonary administration of nanocarriers”

In the paper

“Inhalable nanocarriers of TB drugs have been a major focus of research”

In the paper

“Several oral nanotechnology-based systems have been designed with existing TB drugs and tested in animal models.”

In the paper

“Several of the current antibiotics are poorly soluble”

What the sources say

• Not checked yetcites [120] Jain, R. et al. in Handbook of Nanomaterials for Industrial Applications Ch. 33 (Elsevier, 2018).

In the paper

“and are at risk of developing drug-resistant strains 4 .”

What the sources say

• Not checked yetcites [4] Sabaté, E. Adherence to Long-Term Therapy: Evidence for Action (WHO, 2003).

In the paper

“pulmonary administration of rifampicin-loaded solid lipid nanoparticles in rats enabled delivery to alveolar macrophages 131 .”

What the sources say

• Not checked yetcites [131] Chuan, J. et al. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles. J. Nanopart. Res. 15, 1634 (2013). source

In the paper

“Polymer-based nanoparticles (PLGA and sodium alginate) have also been developed to improve the oral bioavailability of rifampicin, isoniazid, ethambutol, pyrazinamide and streptomycin 124-127 .”

What the sources say

• Not checked yetcites [124] Ahmad, Z. & Khuller, G. Alginate-based sustained release drug delivery systems for tuberculosis. Expert Opin. Drug Deliv. 5, 1323–1334 (2008). source
• Not checked yetcites [125] Pandey, R. & Khuller, G. K. Nanoparticle-based oral drug delivery system for an injectable antibiotic—streptomycin. Evaluation in a murine tuberculosis model. Chemotherapy 53, 437–441 (2007). source
• Not checked yetcites [126] Pandey, R., Zahoor, A., Sharma, S. & Khuller, G. K. Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis. Tuberculosis 83, 373–378 (2003). source
• Not checked yetcites [127] Sharma, A., Pandey, R., Sharma, S. & Khuller, G. K. Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub-therapeutic dose against experimental tuberculosis. Int. J. Antimicrob. Agents 24, 599–604 (2004). source

In the paper

“When guinea pigs were administered an aerosolized formulation of BCG nanomicroparticles, they generated better immune protection and enhanced resistance to TB infection than when they were immunized with the standard parenteral BCG formulation 134 .”

What the sources say

• Not checked yetcites [134] Garcia-Contreras, L. et al. Immunization by a bacterial aerosol. Proc. Natl Acad. Sci. USA 105, 4656–4660 (2008). source

In the paper

“unable to penetrate the alveolar macrophages where the bacilli reside 120 .”

What the sources say

• Not checked yetcites [120] Jain, R. et al. in Handbook of Nanomaterials for Industrial Applications Ch. 33 (Elsevier, 2018).

In the paper

“WHO guidelines recommend treating drug-susceptible TB for at least 6 months with an oral drug regimen of four antibiotics taken daily 11 .”

What the sources say

• Not checked yetcites [11] Treatment of Tuberculosis: Guidelines 4th edn (WHO, 2010); https://www.who.int/tb/publications/2010/9789241547833/en/

In the paper

“bedaquiline was the first new drug approved in more than 40 years (ref. 121 )”

What the sources say

• Not checked yetcites [121] Cohen, J. Approval of novel TB drug celebrated—with restraint. Science 339, 130 (2013). source

In the paper

“Because of the prolonged and frequent dosing, and side effects, patients find it difficult to adhere to these regimens”

What the sources say

• Not checked yetcites [4] Sabaté, E. Adherence to Long-Term Therapy: Evidence for Action (WHO, 2003).

In the paper

“M. tuberculosis (Fig. 7) is the most critical pathogen in the global antimicrobial resistance crisis 119 .”

What the sources say

• Not checked yetcites [119] O’Neill, J. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations (2016).

In the paper

“Solid lipid nanoparticles have been tested in rodents with the goal of improving the bioavailability of rifampicin and the combination of rifampicin, isoniazid and pyrazinamide 122,123 .”

What the sources say

• Not checked yetcites [122] Singh, H., Jindal, S., Singh, M., Sharma, G. & Kaur, I. P. Nano-formulation of rifampicin with enhanced bioavailability: development, characterization and in-vivo safety. Int. J. Pharm. 485, 138–151 (2015). source
• Not checked yetcites [123] Pandey, R., Sharma, S. & Khuller, G. K. Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis 85, 415–420 (2005). source

In the paper

“pulmonary TB is the most common TB form 128 .”

What the sources say

• Not checked yetcites [128] Costa, A. et al. The formulation of nanomedicines for treating tuberculosis. Adv. Drug Deliv. Rev. 102, 102–115 (2016). source

In the paper

“There is no effective vaccine that comprehensively protects against TB infection.”

In the paper

“Pulmonary administration of the common TB antigen 85B conjugated to poly(propylene sulphide) nanoparticles demonstrated improved protection in mice after they were challenged with aerosolized M. tuberculosis (ref. 135 ).”

What the sources say

• Not checked yetcites [135] Ballester, M. et al. Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis. Vaccine 29, 6959–6966 (2011). source

In the paper

“A nano-chitosan-based recombinant DNA vaccine elevated the immunologic and protective effects against TB in a mouse model 136”

What the sources say

• Not checked yetcites [136] Feng, G. et al. Enhanced immune response and protective effects of nano-chitosan-based DNA vaccine encoding T cell epitopes of Esat-6 and FL against Mycobacterium tuberculosis infection. PLoS ONE 8, e61135 (2013). source

In the paper

“However, one currently approved nano-system (an amphotericin B liposomal formulation) is not cost-effective in developing countries 140 .”

What the sources say

• Not checked yetcites [140] Sundar, S. & Jaya, J. Liposomal amphotericin B and leishmaniasis: dose and response. J. Glob. Infect. Dis. 2, 159–166 (2010). source

In the paper

“chitosan has a role as a vaccine adjuvant in the prevention of TB 137 .”

What the sources say

• Not checked yetcites [137] Liu, Q. et al. Preparation and evaluation of antigen/N-trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization. Vaccine 32, 2582–2590 (2014). source

In the paper

“Second, the synthesis and storage conditions of some nanoparticles may not be conducive to conditions in low-resource countries 141 .”

What the sources say

• Not checked yetcites [141] Mitchell, S. L. & Carlson, E. E. Tiny things with enormous impact: nanotechnology in the fight against infectious disease. ACS Infect. Dis. https://doi.org/10.1021/acsinfecdis.8b00138 (2018). source

In the paper

“Subtle changes in process or composition can adversely affect the complex composition of nanomedicines 142,143 .”

What the sources say

• Not checked yetcites [142] Desai, N. Challenges in development of nanoparticle-based therapeutics. AAPS J. 14, 282–295 (2012). source
• Not checked yetcites [143] Ioannidis, J. P. A., Kim, B. Y. S. & Trounson, A. How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation. Nat. Biomed. Eng. 2, 797–809 (2018). source

In the paper

“First, reducing the cost will be the major hurdle in developing new drugs and nanotechnology-based systems.”

In the paper

“Reformulating existing drugs in nanocarriers may help to achieve similar targets of enhanced efficacy and safety at a considerably lower cost.”

In the paper

“These dimensions facilitate better aerosolization compared with particles with similar dimensions in all axes.”

In the paper

“Third, regional and national differences within and between regulatory authorities, especially when running multi-centric international trials, will be a challenge during the clinical trial stage 144 .”

What the sources say

• Not checked yetcites [144] Satalkar, P., Elger, B. S., Hunziker, P. & Shaw, D. Challenges of clinical translation in nanomedicine: a qualitative study. Nanomedicine 12, 893–900 (2016). source