Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs

May combine two claims.

Nanotechnology-based drug delivery is a promising approach for neuro disorders because nanocarriers have been shown to traverse the BBB or BCSFB and deliver drugs within the CNS to the target site.

“Among these methods, nanotechnology-based drug delivery is a quite new as compare to conventional methods and promising approach in the field of neuro disorders, as nanocarriers have been proved efficacious in effectively traversing the BBB or BCSFB and thus effectively delivering drugs within the CNS to the target site (Silva, 2005; Jain, 2007; Wong et al., 2012; Li et al., 2017).”

• cites Silva, 2005Not checked yet

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• cites Jain, 2007Not checked yet

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• cites Wong et al., 2012Not checked yet

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• AssumptionRests on an assumption: Results from preclinical models (mice, cell lines) are predictive of therapeutic outcomes in humans for CNS nanomedicines.

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

Targeted delivery of the drug is a promising approach to minimize the side effects of a therapeutic agent.

“Targeted delivery of the drug is a promising approach to minimize the side effects of a therapeutic agent.”

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

The size, shape, composition, surface charge, monomers molar ratio, solubility of drug, their physiochemical properties, and their release in different acidic and basic environments inside cells play a very important role in the pharmacokinetics of each type of nanocarrier.

“Although it is quite difficult to say which nanoparticulate drug delivery system is having more potential and safe among listed nanocarriers such as polymers, micelles, liposomes, dendrimers, nanocrystals, SLNPs, the size, shape, composition, surface charge, monomers molar ratio, solubility of drug, their physiochemical properties and further their release in different acidic and basic environment”

Probably not a substantial claim: may not pass S2 (checkable).

Nanotechnology is an innovative, promising, and cutting-edge approach for delivering neurotherapeutics across the BBB.

“Nanotechnology is an innovative, promising and cutting edge approach for delivering neurotherapeutics across BBB.”

• cites Kaur et al., 2008Not checked yet

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• AssumptionRests on an assumption: Results from preclinical models (mice, cell lines) are predictive of therapeutic outcomes in humans for CNS nanomedicines.

May combine two claims.

Polymeric micelles are more stable, have longer duration of action, and higher biodistribution than non-polymeric micelles.

“As compared to non-polymeric micelles, polymeric micelles are considered more stable having long duration of action and high biodistribution (Ozkizilcik et al., 2017).”

• cites Ozkizilcik et al., 2017Not checked yet

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May combine two claims.

The complexity of the BBB, high levels of efflux transport proteins including P-glycoproteins (P-gp) and Multidrug Resistant Protein-1 (MRP-1), and expression of metabolic enzymes limit drug entry into the brain.

“The complexity of BBB, the existence of high levels of efflux transport proteins including P-glycoproteins (P-gp) and Multidrug Resistant Protein-1 (MRP-1), and the expression of metabolic enzymes limits the entry of drug inside the brain (Tajes et al., 2014).”

• cites Tajes et al., 2014Not checked yet

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May combine two claims.

Micelles have a core-shell structural design with size ranging from 10 to 100 nm, consisting of an outer hydrophilic environment mostly made of PEG and an inner hydrophobic core, allowing loading of hydrophobic drugs.

“They have a core-shell structural design with size ranging from 10 to 100 nm consisting outer hydrophilic environment mostly made up of polyethylene glycol (PEG) and inner hydrophobic core synthesized by means of molecules such as polycaprolactone, polypropylene glycols, phospholipids, and fatty acids, thus they allow loading of hydrophobic drugs (Torchilin, 2007).”

• cites Torchilin, 2007Not checked yet

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May combine two claims.

Current neurotherapeutics have limited entry into brain cells via the BBB, resulting in insufficient brain entry, and limited access to immune cells in the brain.

“The current neurotherapeutics are associated with two major limitations i.e., before entering into brain cells they are pose to limited entry via BBB as insufficient entry in brain as well as of limited access to immune cells to brain (Misra et al., 2003; Nagpal et al., 2013).”

• cites Misra et al., 2003Not checked yet

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• cites Nagpal et al., 2013Not checked yet

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Classified as probably not a substantial claim.

The selection of an appropriate nanocarrier system is a prerequisite for effective delivery of drug to the CNS across the BBB.

“The selection of an appropriate nanocarrier system is a prerequisite for effective delivery of drug to CNS across BBB.”

May combine two claims.

The drug itself constitutes one part of the nanoengineered complex, while the remaining complex is intended to accomplish other key functions such as encapsulating the active drug, protecting against enzymatic degradation, releasing drug at specific pH, crossing the BBB, and targeting specific brain cells.

“The drug, the pharmacologically active component to be delivered, itself constitutes one part of the nanoengineered complex while remaining complex is intended to accomplish other key functions such as encapsulating the active drug protection against enzymatic degradation, drug release at specific pH, ability to cross the BBB, and targeting specific brain cells (Silva, 2008).”

• cites Silva, 2008Not checked yet

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May combine two claims.

Decorating the delivery system with BBB receptor ligands, coupling antibodies, peptides or aptamers with BBB receptor ligand delivery system, and transporter ligands coupled micelle delivery are approaches for nanocarrier-based brain targeting.

“Decorating the delivery system with BBB receptor ligands, coupling antibodies, peptides or aptamers with BBB receptor ligand delivery system, and transporter ligands coupled micelle delivery are some of the approaches for nanocarriers based brain targeting (Guo et al., 2012; Gao et al., 2013).”

• cites Guo et al., 2012Not checked yet

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• cites Gao et al., 2013Not checked yet

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May combine two claims.

Most drugs used in neural diseases are lipophilic, have molecular weight greater than 400-500 Da, and cannot cross the BBB in pharmacologically significant quantities.

“Most of the drugs used in neural diseases are lipophilic in nature having molecular weight greater 400–500 Da and not able to cross the BBB in pharmacologically significant quantity (Fischer et al., 1998)”

• cites Fischer et al., 1998Not checked yet

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May combine two claims.

SLNs are preferred over polymeric nanoparticles due to advantages including low intrinsic cytotoxicity, physical stability, shielding of labile drugs from degradation, and controlled release, making them potential brain drug delivery systems especially for brain tumors.

“SLNs are preferred more over PNPs due to numerous advantages such as low intrinsic cytotoxicity, physical stability, shielding of labile drugs from degradation, controlled release which provide them potentiality to be used as a brain drug delivery system, especially for brain tumors”

• cites Laquintana et al., 2009Not checked yet

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May combine two claims.

Transferrin receptor-mediated PLGA nanoparticles have better biodistribution in the brain via intranasal administration and are not affected by P-gp pump efflux, enhancing functionalized nanoparticle concentration in the basolateral side after 24 h via receptor-mediated endocytosis.

“They observed that transferring receptor mediated PLGA nanoparticles have better biodistribution in brain via intranasal administration and not affected by P-gP pump efflux enhacing functionalized nanoparticles concentration in the basolateral side after 24 h via receptor mediated endocytosis (Cayero-Otero et al., 2019).”

• cites Cayero-Otero et al., 2019Not checked yet

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May combine two claims.

Polymeric nanoparticles consist of a core of dense polymer matrix to encapsulate lipophilic drugs and a hydrophilic corona to provide steric stability.

“They consists a core of dense polymer matrix to encapsulate the lipophillic drugs and a hydrophilic corona to provide steric stability to NPs.”

• cites Sahoo et al., 2017Not checked yet

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

Liposomes are small spherical vesicles composed of a hydrophilic compartment at the center enclosed by a single or multiple phospholipid bilayers, morphologically resembling the cell membrane, and are used for delivery of drugs, proteins, and peptides.

“These are small spherical vesicles composed of the hydrophilic compartment at the center enclosed by a single or multiple phospholipid bilayers due to which they morphologically resemble with the cell membrane and are used as a strategic approach for drug delivery, proteins and peptides (Martins et al., 2007; Wong et al., 2012; Ozkizilcik et al., 2017).”

• cites Martins et al., 2007Not checked yet

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• cites Wong et al., 2012Not checked yet

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• cites Ozkizilcik et al., 2017Not checked yet

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

Solid-lipid nanoparticles (SLNs) are aqueous colloidal nanocarriers composed of physiological lipids dispersed in water or an aqueous surfactant solution and solidify upon cooling.

“These are aqueous colloidal nanocarriers system which are composed of physiological lipid (triglycerides, fatty acids, steroids, and waxes, etc.), dispersed in water or in an aqueous surfactant solution and possess the ability to get solidify upon cooling”

• cites Barchet and Amiji, 2009Not checked yet

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• cites Mukherjee et al., 2009Not checked yet

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May combine two claims.

Immunoliposome delivery of siRNA against EGFR demonstrated knock-down of EGFR expression and increased survival of mice implanted intracranially with brain tumors.

“This approach has also been used for delivery of small interfering RNA (siRNA) against epithelial growth factor receptor (EGFR) and demonstrated the knock-down of EGFR expression and increased survival of mice implanted intracranially with brain tumors (Pardridge, 2007).”

• cites Pardridge, 2007Not checked yet

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May combine two claims.

The residence time of polymeric nanoparticles in systemic circulation can be increased by surface modification with hydrophilic polymers such as PEGs and polysaccharides, whereas inclusion of tissue-specific ligands facilitates targeted delivery to the brain.

“The residence time of these NPs in systemic circulation can be increased by the surface modification either with physical adsorption or covalent binding of hydrophilic polymers such as PEGs and polysaccharides, whereas the inclusion of tissue-specific ligands facilitates targeted delivery to the brain (Mohamed and Van Der Walle, 2008; Wilson et al., 2008).”

• cites Mohamed and Van Der Walle, 2008 sourceNot checked yet

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• cites Wilson et al., 2008Not checked yet

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

Liposomes were successfully proven as a drug carrier system in the 1970s.

“Liposomes are considered as the first generation of the novel colloidal nanocarriers which were successfully proven themselves as a drug carrier system in the 70’s (Bawarski et al., 2008).”

• cites Bawarski et al., 2008Not checked yet

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May combine two claims.

In mice, intravenous administration of modified micelles loaded with a fluorescent dye or haloperidol resulted in improved delivery of the fluorescent dye to the brain and a drastic increase in the neuroleptic effect of haloperidol.

“In mice, the intravenous administration of these modified micelles after loading with a fluorescent dye or neuroleptic drug haloperidol, resulted in improved delivery of the fluorescent dye to the brain and drastic increase in the neuroleptic effect of haloperidol (Kabanov et al., 1989).”

• cites Kabanov et al., 1989Not checked yet

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May combine two claims.

Modification of SLNs with PEG increases penetration to the blood-brain barrier and enhances drug delivery to the CNS.

“Modification of SLNs with PEG increases penetration to BBB and enhances drug delivery to the CNS as demonstrated by a comparative study of SLNs and PEG-modified SLNs loaded with antitumor drugs like camptothecin and doxorubicin”

• cites Blasi et al., 2007Not checked yet

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• cites Wong et al., 2007Not checked yet

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May combine two claims.

The drug to be delivered may be encapsulated, adsorbed, or chemically linked to the surface of polymeric nanoparticles.

“The drug to be delivered may be encapsulated, adsorbed or chemically linked to the surface of the NPs (Sahoo et al., 2017).”

• cites Sahoo et al., 2017Not checked yet

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May combine two claims.

Pluronic block copolymers have the ability to hinder drug efflux transporters, for instance, inhibiting P-gp efflux transporters widely expressed on the BBB, and enhance drug shipment to the CNS.

“The class of pluronic (also known as Poloxamers) block copolymers is of particular interest as they have an ability to hinder drug efflux transporters, for instance, inhibition of P-gp efflux transporters widely expressed on BBB and enhance drug shipment to the CNS (Batrakova and Kabanov, 2008).”

• cites Batrakova and Kabanov, 2008 sourceNot checked yet

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

Liposomes are reversible structures due to non-covalent interactions such as van der Waals forces and hydrogen bonding between molecules.

“These are reversible structures due to presence of non-covalent interactions such as van der walls forces and hydrogen bonding between molecules (Ramos-Cabrer and Campos, 2013).”

• cites Ramos-Cabrer and Campos, 2013Not checked yet

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May combine two claims.

Transferrin-modified cyclo-(Arg-Gly-Asp-d-Phe-Lys)-Paclitaxel conjugate-loaded micelles demonstrated increased uptake by brain microvascular endothelial cells in vitro, lengthened retention in glioma tumor in vivo, and no considerable toxicity.

“For instance, Zhang et al. (2012) studied transferrin-modified cyclo-(Arg-Gly-Asp-d-Phe-Lys)-Paclitaxel conjugate-loaded micelle and demonstrated the increased uptake by the brain microvascular endothelial cells in vitro in addition to the lengthened retention in glioma tumor in vivo and no considerable toxicity was noticed.”

• cites Zhang et al., 2012Not checked yet

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

Polymeric nanoparticles are solid colloidal dispersions of biodegradable and biocompatible polymers such as PACA, PLA, PLGA, natural proteins, and polysaccharides with size range 10-100 nm.

“Polymeric nanoparticles are solid colloidal dispersion of biodegradable and biocompatible polymers such as poly (alkylcyanoacrylate) (PACA), polyesters such as poly (lactide) (PLA), poly (D,L-lactide-co-glycolic acid) (PLGA), and several others such as natural proteins and polysaccharides with size range 10–100 nm (Kumari et al., 2010).”

• cites Kumari et al., 2010Not checked yet

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May combine two claims.

Coating of PBCA nanoparticles with 1% polysorbate 80 amplified the concentration of rivastigmine or tacrine inside the brain compared with free drug and selectively targeted to the CNS for AD, reducing hepatic or gastrointestinal side-effects.

“It has been established that coating of poly (n-butylcyanoacrilate) (PBCA) NPs with 1% polysorbate 80 (PS80) amplified the concentration of rivastigmine or tacrine drug inside the brain as compared with free drug and selectively targeted to the CNS for AD reducing the hepatic or gastrointestinal side-effects coupled with conventional treatment approach (Wilson et al., 2008).”

• cites Wilson et al., 2008Not checked yet

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May combine two claims.

The external hydrophilic shell provides stability to micelles in an aqueous environment and prolongs their circulation time in the bloodstream, protecting them from the reticulo-endothelial system and facilitating their accumulation in specific regions with leaky vasculature.

“The external hydrophilic shell provides stability to micelles in an aqueous environment and prolongs their circulation time in bloodstream, thus protecting it from reticulo-endothelial system (RES) and further facilitate their accumulation in specific region having leaky vasculature (Park et al., 2008).”

• cites Park et al., 2008Not checked yet

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May combine two claims.

The possible mechanism of SLN delivery across the blood-brain barrier may be endocytosis or transcytosis in endothelial cells lining brain blood capillaries, or permeation through tight junctions between endothelial cells.

“The possible mechanism of their delivery across BBB may be endocytosis, transcytosis which takes place in the endothelial cells lining the blood capillaries in brain or permeation through the tight junctions between endothelial cells.”

May combine two claims.

Conjugation of prednisolone-loaded liposomes with monoclonal antibodies (immunoliposomes) improved distribution of liposomes inside the brain and showed high efficacy against experimental autoimmune encephalomyelitis.

“Conjugation of prednisolone-loaded liposomes with mAbs that will be recognized by cell surface receptors in the targeted tissue called immunoliposomes, demonstrated further improvement in distribution of liposomes inside brain and high efficacy against experimental autoimmune encephalomyelitis (Schmidt et al., 2003).”

• cites Schmidt et al., 2003Not checked yet

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May combine two claims.

Specific ligand transferrin (T7) and non-specific cell penetrating peptide (TAT) conjugated doxorubicin encapsulated liposomes demonstrated high availability across the BBB and specific cell targeting to brain glioma.

“For instance, specific ligand transferrin (T7) and non-specific cell penetrating peptide (TAT) conjugated doxorubicin encapsulated liposomes demonstrated high availability across BBB and specific cell targeting to the brain glioma (Zong et al., 2014).”

• cites Zong et al., 2014Not checked yet

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

Dendrimers have a 3-D symmetrical architecture with an inner core and hyper-branches known as generations, with peripheral functional groups that allow functionalization with different ligands.

“They have 3-D symmetrical architecture possessing an inner core from which a number of hyper-branches, known as “generations,” having various chemical functional groups at the peripheral terminal surface arise due to which they can be easily functionalized with different ligands”

• cites Tripathy and Das, 2013Not checked yet

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• cites Xu et al., 2013Not checked yet

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• cites Leiro et al., 2018Not checked yet

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May combine two claims.

Caveolae are flask-shaped plasma membrane invaginations, and caveolin protein in three isoforms (caveolin-1, caveolin-2, and caveolin-3) plays a dominating role in caveolar transportation.

“Caveolae are flask-shaped plasma membrane invaginations and caveolin protein, present in three isoforms in mammalian cells: caveolin-1, caveolin-2, and caveolin-3 play a dominating role in this transportation pathway”

• cites Kou et al., 2013Not checked yet

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May combine two claims.

Three distinct steps are involved in transcytosis: endocytosis of the nanocarrier at the plasma membrane, trafficking of intracellular vesicles toward the opposite surface, and exocytosis.

“Three distinct steps are involved in overall transcytosis process: endocytosis of the nanocarrier at the plasma membrane, trafficking of intracellular vesicles toward the opposite surface followed by exocytosis”

• cites Rappoport, 2008Not checked yet

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• cites Pardridge, 2012 sourceNot checked yet

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• cites Georgieva et al., 2014Not checked yet

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May combine two claims.

Positive surface charge of nanomaterials interacts with the negative surface charge of brain endothelial cells via electrostatic interactions, and lipophilic nature of nanocarriers enhances adsorption.

“Surface charge like positive nature of the nanomaterials interacts with the negative surface charge of endothelial cells of brain, due to electrostatic interactions between carrier and cells, secondly lipophillic nature of nanocarriers also enhance and facilitates adsorption process”

• cites Markoutsa et al., 2011Not checked yet

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• cites Lien et al., 2012Not checked yet

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May combine two claims.

Adsorbed drug-carrier conjugates are endocytosed by cells, sometimes followed by exocytosis, and further penetrate into cells or brain parenchyma.

“The adsorbed drug–carrier conjugates is endocytosized by the cells, at times followed by exocytosis, and further penetration of the nano carrier into the cells or brain parenchyma occurs.”

• cites Vilella et al., 2014Not checked yet

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

Entry of foreign entities into the CNS is strictly prohibited by the blood-brain barrier, so only selective entities get access to the brain.

“Since the entry of foreign entities in CNS is strictly prohibited by BBB, only selective one gets access to the brain.”

May combine two claims.

Receptor-mediated transcytosis across the blood-brain barrier is an attractive strategy to deliver drugs into the CNS and requires a vector for delivery between apical and basolateral surfaces in polarized cells.

“Transcytosis process especially the receptor-mediated transcytosis across BBB is an attractive strategy to deliver drugs into CNS. It requires vector for the delivery of nanocarrier between the apical and basolateral surface in polarized cells.”

May combine two claims.

Clathrin-mediated endocytosis involves nanocarrier binding to a specific receptor, triggering clathrin-1 polymerization, inward budding, dynamin pinching off to form clathrin-coated vesicles, and eventual degradation in lysosomes with pH-triggered drug release.

“As the nanocarrier binds with a specific receptor on the cell membrane, it triggers the polymerization of clathrin-1, a cytosolic protein underneath the plasma membrane forming an inward budding leading to the internalization of cargo”

• cites Rappoport, 2008Not checked yet

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• cites Pucadyil and Schmid, 2009Not checked yet

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• cites Mellman, 1992Not checked yet

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May combine two claims.

G4HisMal dendrimers have high ability to cross the blood-brain barrier with significant biocompatibility and show memory protection in a transgenic mouse model of Alzheimer disease via synapse protection.

“they were tested it against AD and found their high ability to cross BBB with significant biocompatibility showing memory protection in transgenic mice model of Alzheimer disease via synapse protection”

• cites Aso et al., 2019Not checked yet

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May combine two claims.

In PAMAM-PEG-Doxorubicin conjugates, cisaconityl acid-sensitive linkage follows acid-triggered release kinetics that increases with PEGylation and imparts reduced hepatic and splenic accumulation, prolonged circulation time, and enhanced tumor buildup.

“cisaconityl linkage, an acid-sensitive linkage, in PAMAM-PEG-Doxorubicin (DOX) conjugates followed an acid-triggered release kinetics which gradually increases with increasing degree of PEGylation and simultaneously imparts following properties to the conjugates: reduced hepatic and splenic accumulation, prolonged circulation time, and enhanced tumor buildup”

• cites Zhu et al., 2010a, bNot checked yet

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

Nanotechnology has gained interest for delivery of radiocontrast agents and imaging agents for diagnosis.

“Besides delivery of therapeutic drugs, nanotechnology has also gained the interest of researchers for delivery of radiocontrast agents, imaging agents for diagnosis purpose.”

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

Molecules are nano-engineered to traverse the blood-brain barrier, target specific cells or signaling pathways, and act as carriers for gene delivery.

“Molecules are nano-engineered so that they have an ability to traverse the BBB, target the specific cell or signaling pathway, act as a carrier for gene delivery.”

May combine two claims.

The D-mino dendrimer formulation has high efficacy compared to free drug, decreasing inflammatory cytokines and nitric oxide levels.

“The rapid uptake, decreases inflammatory cytokines and nitric oxide levels suggested that dendrimers formulation are having high efficacy as compare to free drug”

• cites Sharma et al., 2017Not checked yet

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May combine two claims.

The caveolar pathway is similar to the clathrin-mediated pathway but can escape lysosomal delivery, which augments drug delivery at the targeted site and improves therapeutic value.

“This pathway is similar to the clathrin-mediated pathway in most of the aspects but there is possibility to escape lysosomal delivery which is a key factor that makes it different from the clathrin-mediated pathway”

• cites Mcintosh et al., 2002Not checked yet

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May combine two claims.

Fabrication of nanoemulsions with oils rich in omega-3 polyunsaturated fatty acids imparts properties for overcoming biological barriers including the blood-brain barrier and helps rapid distribution of drugs to peripheral sites, especially the brain.

“fabrication of nanoemulsions with oils that are rich in omega-3 polyunsaturated fatty acids (PUFA) imparts specific properties to nanocarriers for overcoming biological barrier, including the BBB, therefore help in achieving the rapid distribution of drugs to peripheral sites, especially the brain”

• cites Shah et al., 2013Not checked yet

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May combine two claims.

Nanoemulsions as drug delivery systems tackle problems such as low bioavailability, poor targetability, and poor penetrability across the blood-brain barrier.

“Recently, their use as drug delivery system has been promoted heavily to tackle several problems associated with conventional delivery systems such as low bioavailability, poor targetability, and penetrability across BBB”

• cites Lovelyn and Attama, 2011Not checked yet

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

Nanoemulsions are oil-in-water or water-in-oil colloidal particulate systems composed of edible oils, surfactants and water, with a size range of 100-500 nm.

“Nanoemulsions are either oil-in-water (O/W) or water-in-oil (W/O) colloidal particulate systems that are composed of edible oils, surface-active agents (surfactants) and water, having a size range 100–500 nm”

• cites Sarker, 2005Not checked yet

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• cites Lovelyn and Attama, 2011Not checked yet

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May combine two claims.

Nanocarriers enter the brain either by passive, gradient-dependent passive targeting or active, energy-dependent active targeting pathways.

“They get entry into the brain either by passive, gradient-dependent (passive targeting) or active, energy-dependent (active targeting) pathways.”

May combine two claims.

Pathology of Parkinson disease involves various other brain regions, neurotransmitter imbalance in acetylcholine and dopamine, and protein aggregates other than Lewy bodies.

“pathology of PD is not just limited to a particular part of the brain but it involves various other regions of the brain, neurotransmitters such as imbalance in ACh and dopamine, and protein aggregates other than Lewy bodies”

• cites Kalia and Lang, 2015Not checked yet

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

Manifestations of Parkinson disease involve motor symptoms like tremor, speech, writing changes and non-motor symptoms like cognitive, behavioral, and autonomic changes.

“The manifestations of PD involve motor symptoms like tremor, speech, writing changes and non-motor symptoms like cognitive, behavioral, and autonomic changes.”

May combine two claims.

PEG stabilized nanomicelles composed of phospholipids inhibit Aβ aggregation and attenuate Aβ-induced neurotoxicity in SHSY-5Y human neuroblastoma cell line in vitro.

“It was demonstrated that PEG stabilized nanomicelles composed of phospholipids inhibit Aβ aggregation and attenuate Aβ-induced neurotoxicity in SHSY-5Y human neuroblastoma cell line in vitro”

• cites Pai et al., 2006Not checked yet

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May combine two claims.

Fullerene's ability for neuroprotection against Aβ toxicity in vitro and in vivo has not been proved, but its ability to inhibit Aβ peptide fibrillization and prevent Aβ-induced cognitive impairments after intraventricular administration suggests a beneficial role in Alzheimer disease treatment.

“On the other hand ability of fullerene for neuroprotection, in vitro as well as in vivo, against Aβ toxicity has not been proved, yet its ability to inhibit Aβ peptide fibrillization and prevention of Aβ-induced cognitive impairments after intraventricular administration suggests its beneficial role in AD treatment”

• cites Podolski et al., 2007Not checked yet

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

The prevalence rate of multiple sclerosis ranges from 2 to 150 per 100,000 people, and females are more susceptible than males.

“The prevalence rate of MS ranges 2–150 per 100,000 people and females are more susceptible than males”

• cites Jones et al., 2008Not checked yet

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

Multiple sclerosis is a progressive autoimmune and inflammatory disease in which the body's immune cells attack the nervous system.

“Multiple sclerosis (MS) is a progressive autoimmune and inflammatory disease. It is a multifactorial disease in which body’s immune cells attack on the nervous system.”

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

Nitrendipine is a calcium channel blocker that declines the incidences of dementia up to 50% in Huntington disease over a period of 2 years.

“Nitrendipine is a calcium channel blocker that declines the incidences of dementia (upto 50%) in HD in a period of 2 years.”

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

Multiple sclerosis involves pathogenic mechanisms leading to demyelination of myelinated axons, resulting in slow conduction of nerve signals.

“It involves various pathogenic mechanisms leading to demyelination of myelinated axons which results into slow conduction of nerve signal.”

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

Alzheimer disease is a slowly progressive neurodegenerative disorder and is the main culprit for dementia syndrome.

“Alzheimer’s disease is a slowly progressive neurodegenerative disorder, and is the main culprit for dementia syndrome.”

• cites Sloane et al., 2002Not checked yet

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May combine two claims.

A nanoliposomal formulation of curcumin enhances its bioavailability without disturbing its ability to inhibit Aβ aggregation.

“The nanoliposomal formulation of curcumin enhanced its bioavailability without disturbing its ability of inhibiting Aβ aggregation”

• cites Taylor et al., 2011Not checked yet

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May combine two claims.

Brains of Huntington disease patients and mouse models demonstrate accumulation of mutant huntingtin in striatal astrocytes, leading to age-dependent Huntington-like pathology and premature mortality.

“Brains of HD patients and mouse models of HD demonstrates accumulation of mutant HTT in striatal astrocytes which ultimately leads to age-dependent HD-like pathology and premature mortality”

• cites Bradford et al., 2009Not checked yet

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

Multiple sclerosis is diagnosed on the basis of clinical findings, magnetic resonance imaging, and examination of cerebrospinal fluid.

“It is diagnosed on the basis of clinical findings, magnetic resonance imaging (MRI) and examination of Cerebrospinal fluid (CSF)”

• cites Khare et al., 2014Not checked yet

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May combine two claims.

Increased levels of metal ions such as copper contribute to Alzheimer disease pathology, and chelating agents are an approach for Alzheimer disease management.

“Since the increased level of metal ions, such as copper, also contributes in the pathology of AD, use of chelating agents is another approach for AD management”

• cites Lovell et al., 1998Not checked yet

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May combine two claims.

PEG and polyethyleimine nanogel complexes with antisense oligonucleotides cross the blood-brain barrier in vitro and deliver oligonucleotides to the brain when injected intravenously, more efficaciously when functionalized with insulin or transferrin molecules.

“The PEG and polyethyleimine nanogels complexes with antisense oligonucleotides demonstrated the efficient crossing of BBB in vitro and also delivered the oligonucleotides to the brain, when injected intravenously, more efficaciously particularly when the gels were functionalized with insulin or Tf molecules”

• cites Vinogradov et al., 2004Not checked yet

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May combine two claims.

Microemulsion nanoparticles loaded with copper chelator d-penicillamine cross the blood-brain barrier and dissolve pre-existing Aβ aggregates in vitro.

“Microemulsion nanoparticles loaded with copper chelator d-penicillamine were found to have capability of crossing the BBB and dissolving the pre-existing Aβ aggregates in vitro”

• cites Cui et al., 2005Not checked yet

  Not checked in the free run.

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

Degeneration of nervous tissue in Alzheimer disease starts years before the actual appearance of symptoms.

“The degeneration of nervous tissue in AD starts years back of the actual appearance of the symptoms of the disease.”

May combine two claims.

Nitrendipine is hydrophilic, has permeability issues, and poorly crosses the blood-brain barrier.

“Being hydrophilic, this drug has permeability issues and thus poorly crosses BBB.”

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

Parkinson disease is illustrated by loss of dopaminergic neurons in the substantia nigra and generation of α-synuclein aggregates (Lewy bodies), and is the next most common neurodegenerative disorder worldwide after Alzheimer disease.

“Parkinson’s disease, illustrated by loss of dopaminergic neurons in the substantia nigra of the midbrain and the generation of α-synuclein aggregates (Lewy bodies), is the next most common neurodegenerative disorder worldwide after AD.”

• cites Kalia and Lang, 2015Not checked yet

  Not checked in the free run.

May combine two claims.

mPEG PLGA nanoparticles of size 70 nm encapsulating Schisantherin A extend SA circulation in the blood stream, increase brain uptake, and are potentially efficacious for Parkinson disease.

“mPEG PLGA nanoparticles of size range 70 nm i.e., Schisantherin A (SA) was used against Parkinson diseases (PD) in zebrafish larvae where SA encapsuled in nanoparticles formulation that extended SA circulation in the blood stream and consequently an increased brain uptake and reported as potentially efficacious for the treatment of PD”

• cites Chen et al., 2017Not checked yet

  Not checked in the free run.

May combine two claims.

Nanotechnological approach has shown great potential to reverse or limit disease states, promote functional regeneration of damaged neurons, provide neuroprotection, and facilitate drug delivery overcoming the blood-brain barrier.

“This problem can be addressed by the nanotechnological approach, as it has shown great potential to reverse or limit the disease states, promote the functional regeneration of damaged neurons, provide neuroprotection and facilitate the delivery of drugs overcoming the BBB”

• cites Modi et al., 2010Not checked yet

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• cites Soursou et al., 2015Not checked yet

  Not checked in the free run.

May combine two claims.

Oxidative damage is a key factor in Alzheimer disease pathology, suggesting applications of antioxidants in Alzheimer disease management.

“Oxidative damage, another key factor in the pathology of AD, suggests the applications of antioxidants in AD management.”

May combine two claims.

Fullerene derivatives are potent free-radical scavengers and possess neuroprotective action against glutamate receptor-induced excitotoxicity.

“Fullerene derivatives, the potent free-radical scavengers, have been found to possess neuroprotective action against glutamate receptors induced excitotoxicity.”

• cites Podolski et al., 2007Not checked yet

  Not checked in the free run.

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

Evidence suggests mutual interplay of microglial, astrocyte and T-cells beside demyelination in multiple sclerosis.

“There are evidences which suggest mutual interplay of microglial, astrocyte and T-cells beside demyelination”

• cites Khare et al., 2014Not checked yet

  Not checked in the free run.

• cites Ojha and Kumar, 2018Not checked yet

  Not checked in the free run.

May combine two claims.

In diseased conditions, glial activation leads to neuroinflammation and imbalance between pro-inflammatory and anti-inflammatory cytokines; nanoformulations stabilize and modulate drug release to cross the blood-brain barrier and restore healthy conditions by reducing neuroinflammation and glial cell activation.

“when an external stumuli or in diseased conditions glial activation occurs which leads to neuroinflammation and leads to imbalance between pro-inflammatory and (IL-1β, TNF-α, and IL-6) and anti-inflammatory cytokines (IL-4, IL-10, etc.), here the authors are showing through schematic representation that drugs loaded with nanoformulations such as immunoliposomes, dendrimers, micelles, liposomes, a”

May combine two claims.

Huntington disease occurs due to a monogenic mutation in exon 1 of the huntingtin gene leading to polyglutamine expansion and misfolding and aggregation of huntingtin protein in the brain.

“It occurs due to monogenic mutation in the exon 1 of huntingtin gene which leads to polyglutamine (poly Q) expansion and causes misfolding and aggregation of huntingtin protein (HTT) in the brain”

• cites Bates et al., 2015 sourceNot checked yet

  Not checked in the free run.

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

Amyloid-β plaques and Tau protein hyper-phosphorylation are considered hallmarks of Alzheimer disease.

“Amyloid-β plaques and Tau protein hyper-phosphorylation are considered as hallmarks of AD”

• cites Kumar and Singh, 2015 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Fullerenols have the ability to clear free radicals and reduce oxidative burden to cells.

“Fullerenols have ability to clear free radicals and reduce oxidative burden to cell.”

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

Huntington disease is described by preferential loss of neurons in the striatum and other brain regions leading to progressive motor, cognitive, and psychiatric manifestations.

“Huntington disease (HD) is described by preferential loss of neurons in striatum and other brain regions leading to progressive motor, cognitive, and psychiatric manifestations.”

May combine two claims.

Curcumin reduces Aβ oligomerization and cytotoxicity in vitro but has poor bioavailability when injected into mice.

“The in vitro study demonstrated the ability of phytochemical curcumin to reduce Aβ oligomerization and cytotoxicity, but poor bioavailability was shown when injected into mice”

• cites Yang et al., 2005 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Conventional gene delivery studies involve viral vectors commonly associated with toxicity and immunogenicity, while nanotechnological approach is devoid of such problems.

“The conventional gene delivery studies involve viral vectors, but they were commonly associated with toxicity and immunogenicity problems while nanotechnological approach was found to be devoid of such type of problems”

• cites Witt and Marks, 2011Not checked yet

  Not checked in the free run.

May combine two claims.

Fullerenols have antagonistic behavior on glutamate receptors and can be implicated for neuroprotective use.

“Jin et al reported their antagonistic behavior on glutamate receptors and therefore they can be implicated for neuroprotective use”

• cites Jin et al., 2000Not checked yet

  Not checked in the free run.

May combine two claims.

Brain tumors are among the most challenging diseases to treat due to poor prognosis, diagnosis, high recurrence rate, and limited methods to transport anti-cancer drugs across the blood-brain barrier in effective concentration.

“They are among the most challenging disease to treat due to poor prognosis, diagnosis, high recurrence rate, and availability of limited number of convenient methods to transport anti-cancer drugs across BBB in effective concentration”

• cites Sanai and Berger, 2008Not checked yet

  Not checked in the free run.

• cites Özdemir et al., 2017Not checked yet

  Not checked in the free run.

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

Brain tumors may be benign or metastatic, and glioblastoma multiforme is the most prevalent malignant glioma.

“Brain tumors, like other body parts tumors, may be benign, originating and residing within the brain, or metastatic, originating from a tumor outside the CNS, among which glioblastoma multiforme (GBM) – a malignant glioma, is the most prevalent.”

• cites Sanai and Berger, 2008Not checked yet

  Not checked in the free run.

• cites Özdemir et al., 2017Not checked yet

  Not checked in the free run.

May combine two claims.

Current treatments for brain tumors are palliative, involving surgical debulking with radiotherapy and chemotherapy, are not sufficient for complete treatment, and reversal to the tumor state is common.

“Current treatments available are just palliative, involving united approaches of surgical debulking with radiotherapy and chemotherapy, which are not sufficient for the complete treatment, and also the reversal to the tumor state again is most common”

• cites Özdemir et al., 2017Not checked yet

  Not checked in the free run.

May combine two claims.

Nanoparticles as contrast agents offer detailed cellular and molecular imaging and provide information for efficient surgical removal of gliomas.

“For imaging purpose, NPs as contrast agents offer detailed cellular and molecular imaging and thus provide information for efficient surgical removal of gliomas.”

May combine two claims.

Fullerenols act as antioxidants and free radical scavengers and are capable of reducing glutamate-, NMDA-, AMPA-, and kainite-induced excitotoxicity and apoptosis.

“Fullerenols, hydroxyl functional group possessing fullerene derivatives, have been demonstrated to act as an antioxidant and free radical scavenger, due to which they are capable of reducing glutamate, N-methyl-d-aspartate (NMDA), Amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), and kainite induced excitotoxicity and apoptosis.”

• cites Jin et al., 2000Not checked yet

  Not checked in the free run.

• cites Dugan et al., 2001Not checked yet

  Not checked in the free run.

May combine two claims.

Xenon gas readily crosses the blood-brain barrier and has favorable neuroprotective properties; xenon-loaded liposomes administered up to 5 h after stroke onset at 7-14 mg/kg diminish infarct size in a rat model.

“xenon gas, a small molecule that can readily cross the BBB and has favorable neuroprotective properties, was loaded into liposomes and administered for up to 5 h after stroke onset with an optimal dosage range of 7–14 mg/kg and found to diminish infarct size in a rat model”

• cites Peng et al., 2013Not checked yet

  Not checked in the free run.

May combine two claims.

Curcumin's clinical implication is hindered by low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetics.

“Despite the wide medicinal applications of curcumin, its clinical implication is hindered due to low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetic (Chattopadhyay et al., 2008).”

• cites Chattopadhyay et al., 2008Not checked yet

  Not checked in the free run.

May combine two claims.

Fullerenol-mediated neuroprotection is suggested to occur through inhibition of glutamate channels without affecting GABA(A) or taurine receptors and by lowering glutamate-mediated intracellular calcium concentrations.

“The ability of these nano-structures to inhibit glutamate channels without affecting GABA (A) or taurine receptors as well as their capability to lower the glutamate-mediated intracellular calcium concentrations are the suggested mechanisms for fullerenol mediated neuroprotection (Jin et al., 2000; Dugan et al., 2001).”

• cites Jin et al., 2000Not checked yet

  Not checked in the free run.

• cites Dugan et al., 2001Not checked yet

  Not checked in the free run.

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

Ischemic stroke contributes 87% of total stroke and comprises lacunar, cardioembolic and cryptogenic stroke; hemorrhagic stroke contributes 13%, comprising 10% intracerebral and 3% hemorrhagic.

“Ischemic stroke, contributing 87% of total stroke, comprising of lacunar, cardioembolic and cryptogenic stroke, and the hemorrhagic stroke, having 13% contribution to the total stroke, comprising of 10% intracerebral and 3% hemorrhagic stroke”

• cites Sacco et al., 2013 sourceNot checked yet

  Not checked in the free run.

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

Epilepsy is a CNS disorder characterized by an abnormal increase in brain electrical activity that may be limited to the focal area or spread throughout the brain, resulting in partial or generalized seizures.

“Epilepsy, a CNS disorder, is characterized by an abnormal increase in brain electrical activity that may be either limited to the focal area or spread throughout the brain, resulting in partial or generalized seizures, respectively”

• cites Jabir et al., 2015Not checked yet

  Not checked in the free run.

May combine two claims.

Gefitinib inhibits EGFR signaling and blocks autophosphorylation of critical tyrosine residues on EGFR, whereas GOLPH3 siRNA downregulates GLOPH3 expression.

“Gefitinib can inhibit EGFR signaling and block the autophosphorylation of critical tyrosine residues on EGFR whereas GOLPH3 siRNA downregulate GLOPH3 expression”

• cites Ye et al., 2019Not checked yet

  Not checked in the free run.

May combine two claims.

Biodegradable PLGA-curcumin is non-toxic in human neuroblastoma SK-N-SH cells and protects from H2O2-induced rise in ROS.

“Exhibit non-toxicity in human neuroblastoma SK-N-SH cells and protect from H2O2- induced rise in ROS.”

• cites Doggui et al., 2012Not checked yet

  Not checked in the free run.

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

Glioma cells aggressively infiltrate normal brain tissue and survive exposure to current adjuvant therapies, making it important to construct specific targeted nanoplatforms capable of delivering imaging agents directly into invasive tumor cells.

“Owing to the ability of glioma cells to aggressively infiltrate normal brain tissue and survive from the exposure to current adjuvant therapies, it is extremely important to construct specific targeted nanoplatforms capable of delivering imaging agents directly into invasive tumor cells.”

May combine two claims.

DNA-carrier gold nanoparticle based barcode assay is highly sensitive to detect biomarkers in cerebrospinal fluid or diseased brain and may be useful in diagnosis of multiple sclerosis.

“DNA-carrier gold NPs based barcode assay is highly sensitive assay to detect biomarkers in CSF or diseased brain. Since radio diagnosis is a gold technique for detection of MS, this diagnostic assay may be highly useful in diagnosis of MS”

• cites Georganopoulou et al., 2005Not checked yet

  Not checked in the free run.

May combine two claims.

Curcumin has been found to possess many pharmacological activities including anti-inflammatory, antimicrobial, anticancer, and neuroprotective effects in neurodegenerative disorders in preclinical and clinical studies.

“Being a natural antioxidant, curcumin has been found to possess many pharmacological activities including anti-inflammatory, antimicrobial, anticancer, the neuroprotective effect in neurodegenerative disorders (Table 5), in both preclinical and clinical studies.”

• cites Chattopadhyay et al., 2008Not checked yet

  Not checked in the free run.

May combine two claims.

CNTF loaded microcapsules demonstrate in situ sustained delivery of CNTF upon encapsulation into polymers and are devoid of immune response and cytotoxic effect.

“ciliary neurotrophic factor (CNTF) loaded microcapsules demonstrated in situ sustained delivery of CNTF upon encapsulation into polymers. This formulation was found to be devoid of any immune response and cytotoxic effect”

• cites Aebischer et al., 1996Not checked yet

  Not checked in the free run.

May combine two claims.

Biodegradable PLGA-curcumin prevents induction of the redox-sensitive transcription factor Nrf2 in the presence of H2O2, indicating protection against oxidative injury in AD.

“Able to prevent the induction of the redox-sensitive/transcription factor Nrf2 in the presence of H2O2, indicative approach to protect neurons against oxidative injury that is usually observed in AD”

• cites Doggui et al., 2012Not checked yet

  Not checked in the free run.

May combine two claims.

Cerium oxide nanoparticles possess antioxidant properties that support cell survival and reduce production of free radicals, and are non-toxic to neuronal (HT22) and macrophage (RAW164) cell lines.

“Cerium oxide nanoparticles were demonstrated to possess antioxidant properties that supported cell survival and reduced the production of free radicals, as well as, were found to be non-toxic to neuronal (HT22) and macrophage (RAW164) cell lines”

• cites Schubert et al., 2006Not checked yet

  Not checked in the free run.

May combine two claims.

Methotrexate conjugated to polyether-copolyester dendrimers demonstrates improved cytotoxicity against U87 and U343 cancer cell lines in culture and overcomes acquired resistance to the drug.

“Methotrexate conjugated to polyether-copolyester (PEPE) dendrimers demonstrated improved cytotoxicity against U87 and U343 cancer cell lines in culture and this nanoformulation was able to overcome acquired resistance to the drug”

• cites Dhanikula et al., 2008Not checked yet

  Not checked in the free run.

May combine two claims.

PEG-coated hexadecyl cyanoacrylate nanoparticles encapsulating an antineoplastic drug show controlled drug release kinetics and higher diffusion of drug across the blood-brain barrier compared to bulk drug in a rat model of gliosarcoma.

“They observed controlled drug release kinetics along with higher diffusion of drug across BBB as compared to bulk drug in a rat model of gliosarcoma”

• cites Brigger et al., 2002Not checked yet

  Not checked in the free run.

May combine two claims.

Nanotechnological approach has shown great potential to overcome major hurdles in stroke management and provides a useful platform for development of novel therapeutic methods.

“The nanotechnological approach has shown great potential to overcome the major hurdles in stroke management and has provided a useful platform for the development of novel therapeutic methods for treatment”

• cites Sarmah et al., 2017Not checked yet

  Not checked in the free run.

May combine two claims.

The problems of curcumin delivery can be solved by developing an efficient delivery system, and nanotechnology provides a platform to handle the hurdles for efficient delivery and action of curcumin.

“However, these problems can be solved by developing efficient delivery system, and the nano-technological approach has provided a platform to handle all the hurdles for the efficient delivery and action of curcumin (Naksuriya et al., 2014).”

• cites Naksuriya et al., 2014Not checked yet

  Not checked in the free run.

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

Stroke is an acute CNS disorder characterized by disruption to the vasculature supplying the brain, resulting in sudden symptoms within seconds to hours depending on the fraction of the brain involved and the severity.

“Stroke, an acute CNS disorder, is characterized by the disruption to the vasculature supplying the brain, resulting into sudden symptoms, within seconds to hours, which usually depends on the fraction of the brain involved and the severity.”

May combine two claims.

Effective neuroprotection and promotion of vascular regeneration in ischemic brain have been achieved by treatment with VEGF-loaded transferrin-modified liposomes (Tf-LPs).

“Thus, effective neuroprotection and promotion of vascular regeneration in the ischemic brain have been achieved by treatment with VEGF loaded transferrin-modified liposomes (Tf-LPs).”

• cites Zhao et al., 2010Not checked yet

  Not checked in the free run.

• AssumptionRests on an assumption: VEGF participates in post-ischemic brain repair via promoting neurogenesis and cerebral angiogenesis and is potentially useful to attenuate ischemic brain injury.

May combine two claims.

Increased surface area results in augmented chemical reactivity of nanoparticles, which increases ROS production and leads to toxicity such as neuroinflammation, excitotoxicity, DNA damage, and allergic responses.

“The increased surface area results in an augmented chemical reactivity of the nanoparticles which then increase the production of ROS and ultimately leads to toxicity, such as neuroinflammation, excitotoxicity, DNA damage and allergic responses.”

May combine two claims.

PEG-liposomes with anti-transferrin, lipid conjugate liposome, nanoliposomes, and PEG-polylactic acid block copolymer inhibit Aβ aggregation.

“Aggregation inhibition of Aβ”

• cites Mourtas et al., 2014Not checked yet

  Not checked in the free run.

May combine two claims. The quote only partly states this claim.

Water-soluble PLGA-coated curcumin NPs coupled with Tet-1 peptide successfully destroy amyloid aggregates and have anti-oxidative and non-cytotoxic properties.

“They found that curcumin encapsulated NPs successfully destroyed amyloid aggregates along with anti-oxidative property and non-cytotoxicity (Mathew et al., 2012).”

• cites Mathew et al., 2012Not checked yet

  Not checked in the free run.

May combine two claims.

PLGA-b-PEG-TPP-based curcumin nanoformulation shows significant cytosolic and mitochondrial fractions in cells, indicating mitochondria-targeting chemotherapeutics.

“Confirmed significant cytosolic and mitochondrial fractions in cells, indicating mitochondria-targeting chemotherapeutics”

• cites Marrache and Dhar, 2012Not checked yet

  Not checked in the free run.

May combine two claims.

Poly(N-isopropyl acrylamide)-curcumin nanoformulation improves neurobehavioral activity, reduces cytokine levels (TNF-α and IL-1β), and reduces oxidative stress.

“Improved neurobehavioral activity and reduced cytokine levels (tumor necrosis factor alpha (TNF-α) and IL-1β) and reduces oxidative stress”

• cites Ahmad et al., 2016Not checked yet

  Not checked in the free run.

May combine two claims.

CPC nanoparticles improve behavior disorder and dopamine depletion in MPTP-induced PD mice after treatment at 15 mg curcumin/kg.

“Furthermore, they observed improved behavior disorder along with dopamine depletion after treatment with CPC NPs (15 mg curcumin/kg) (Nisi Zhang et al., 2018).”

• cites Nisi Zhang et al., 2018Not checked yet

  Not checked in the free run.

May combine two claims.

Iron oxide nanoparticles conjugated to NGF stabilize NGF and enhance neuronal differentiation.

“Stabilize NGF and enhance neuronal differentiation”

• cites Marcus et al., 2015Not checked yet

  Not checked in the free run.

• AssumptionRests on an assumption: NGFs are needed for development and phenotype maintenance of neurons in the peripheral nervous system and for functional integrity of neurons in the CNS, and have therapeutic potential for various CNS disorders.

May combine two claims.

Intraperitoneal injection of NanoCurcTM at 25 mg/kg twice daily in athymic mice demonstrates significant curcumin levels in the brain and results in decreased H2O2 and caspase activities along with increased glutathione concentrations.

“In vivo, intraperitoneal (IP) injection of NanoCurcTM at a dose of 25 mg/kg twice daily in athymic mice demonstrated significant curcumin levels in the brain and resulted in decreased levels of H2O2, and caspases activities in brain along with increased glutathione concentrations (Ray et al., 2011).”

• cites Ray et al., 2011Not checked yet

  Not checked in the free run.

May combine two claims.

Solid-LNS shows elevated cellular uptake and better neuroprotective effect compared to edaravone in SH-SY5Y695 cell line.

“Solid-LNS showed elevated cellular uptake and better neuroprotective effect compared to EDR in SH-SY5Y695 cell line (Parikh et al., 2017).”

• cites Parikh et al., 2017Not checked yet

  Not checked in the free run.

• AssumptionRests on an assumption: No oral formulation of edaravone is currently available; only an intravenous liquid formulation is commercially available.

May combine two claims.

Curcumin-gold nanoparticles interact with amyloid protein/peptide and diminish amyloid fibrillation and dissolve amyloid fibrils by acting as artificial molecular chaperones.

“Interacted with amyloid protein/peptide and simultaneously diminish amyloid fibrillation and dissolve amyloid fibrils by acting as artificial molecular chaperones”

• cites Palmal et al., 2014Not checked yet

  Not checked in the free run.

May combine two claims.

Nanoparticles functionalized with specific ligands provide successful drug targeting, but their extremely small size and large surface area may cause particle aggregation, interparticular friction, limited drug loading, and high clearance rate sufficient to preclude their use in diagnosis and drug delivery.

“Although, nanoparticles functionalized with specific ligands provide successful drug targeting, but their extremely small size and the large surface area may cause problems like particle aggregation, interparticular friction, limited drug loading and high clearance rate sufficient to preclude their use in diagnosis and drug delivery.”

May combine two claims.

Anti-amyloid antibody-conjugated curcumin/dexamethasone loaded gadolinium/magnetic nanoparticles enable early diagnosis, effective targeting, and therapeutic action against cerebrovascular amyloid.

“Early diagnosis, effective targeting, and as a therapeutic agent(s) of cerebrovascular amyloid”

• cites Jaruszewski et al., 2014 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Curcumin-loaded polysorbate 80 modified cerasome (CPC) nanoparticles have better stability, longer circulation time, and higher permeation than bulk curcumin.

“They reported better stability, longer circulation time, and higher permeation of nanoformulation of curcumin as compared to bulk curcumin.”

• cites Nisi Zhang et al., 2018Not checked yet

  Not checked in the free run.

May combine two claims.

Curcumin-loaded PLGA-PEG nanoparticles diffuse effectively through brain parenchyma and provide neuroprotection against impaired blood-brain barrier in regions of injury in neonatal rat brain.

“They observed neuroprotection against impaired blood–brain barrier in regions of injury. These nanoparticles diffuses effectively through the brain parenchyma (Joseph et al., 2018).”

• cites Joseph et al., 2018Not checked yet

  Not checked in the free run.

The quote only partly states this claim.