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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with memory and cognitive impairment. Donepezil is an acetylcholinesterase inhibitor used for the symptomatic treatment of AD. However, high dose of donepezil is prescribed to achieve effective concentration in the brain, which leads to significant side effects, gastrointestinal alterations, and hepatotoxicity. In the present study, ApoE3 conjugated polymeric nanoparticles derived from diblock copolymer methoxy poly­(ethylene glycol)–polycaprolactone (mPEG–PCL) have been used to boost the delivery of donepezil to the brain. mPEG–PCL is an amphiphilic diblock polymer with a tendency to avoid nanoparticle uptake by phagocytic cells in the liver and can significantly reduce the gastric mucosal irritations. Moreover, ApoE3-based nanocarriers showed a promising ability to enhance brain uptake, binding to amyloid beta with high affinity and accelerating its clearance. Donepezil-loaded polymeric nanoparticles were performed by using a nanoprecipitation method and further surface modified with polysorbate 80 and ApoE3 to increase the brain bioavailability and reduce the dose. Optimization of various process parameters were performed using quality by design approach. ApoE3 polymeric nanoparticles were found to be stable in simulated gastric fluids and exhibited a sustained drug release pattern. Cellular uptake studies confirmed better neuronal uptake of the developed formulation, which is further corroborated with pharmacokinetic and biodistribution studies. Orally administered ApoE3 polymeric nanoparticles resulted in significantly higher brain donepezil levels after 24 h (84.97 ± 11.54 ng/mg tissue) as compared to the pure drug (not detected), suggesting a significant role of surface coating. Together, these findings are promising and offer preclinical evidence for better brain availability of donepezil by oral administration.

Babchi essential oil (BEO) is a valuable essential oil reported to possess a variety of biological activities such as antitumor, anti inflammatory, immunomodulatory, antioxidant, antifungal and antibacterial properties. Due to its anti-microbial properties, this oil possesses an immense potential for the treatment of dermatological disorders. Further, it has minimal tendency to develop resistance, a common issue with most of the antibiotics. However, its highly viscous nature and poor stability in the presence of light, air and high temperature, limits its practical applications. To surmount these issues, this research aims to encapsulate BEO in ethyl cellulose (EC) microsponges for enhanced stability, antibacterial effect and decreased dermal toxicity. The quasi emulsion solvent evaporation technique was used for fabrication of the BEO microsponges employing EC as polymer, polyvinyl alcohol (PVA) as stabilizer and dichloro methane (DCM) as solvent. The effect of formulation variables such as the amount of EC and PVA were also investigated. The prepared microformulations were evaluated for production yield, encapsulation efficiency, particle size and in vitro release. In vitro cytotoxicity was also checked to assess dermal safety of BEO microsponges. Results revealed that all the dispersions were in micro size range (20.44 ± 3.13 μmto 41.75 ± 3.65 μm), with good encapsulation efficiency (87.70 ± 1.20% of F2) and controlled release profile (cumulative drug release 73.34 ± 1.76%). Field emission scanning electron microscopy results showed that the microsponges possessed a spherical uniform shape with a spongy structure. Results of cytotoxicity study indicated that the prepared microsponges were safer on dermal cells in comparison to pure BEO. The optimized formulation was also evaluated for in vitro antimicrobial assay against dermal bacteria like Staphylococcus aureus , Pseudomonas aeruginosa and Escherichia coli , which confirmed their enhanced antibacterial activity. Furthermore, the results of photostability and stability analysis indicated improved stability of BEO loaded microsponges. Hence, encapsulation of BEO in microsponges resulted in efficacious carrier system in terms of stability as well as safety of this essential oil along with handling benefits.

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A reliable and sensitive UPLC-MS/MS based method has been developed for the estimation of 4-hydroxyisoleucine, a potent insulinotropic and hypolipidemic agent.

Trigonelline is a quaternary base alkaloid and zwitterionic complex that acts by affecting β‐cell regeneration and insulin secretion. Tr inhibits enzymatic activities, lowering the blood glucose and lipid levels due to which it is used in the treatment of co‐morbid diseases such as diabetes, Alzheimer's, etc. Herein, it was aimed to develop a bioanalytical method for estimation of Tr using ultra‐performance liquid chromatography–tandem mass spectrometry and explore the pharmacokinetic profile. The anti‐diabetic, antilipidemic efficacy studies of Tr in the high‐fat diet‐induced streptozotocin‐diabetic rat model was also explored. The separation of analyte was achieved with acetonitrile and 0.1% formic acid (20:80) with a flow of 0.4 mL/min. The ionization of the analyte was achieved in positive electrospray ionization mode with the precursor to product ion transitions of Tr (138.14 > 94), and Trigonelline D3 (143.19 > 97.13). The validated assay was effectively applied for the estimation of compartmental pharmacokinetic by using Phoenix WinNolin8.0 (Certera™, USA) and it was observed that the Tr follow two compartmental pharmacokinetic model. The experimental results also suggest that Tr distributed through the central compartment to the peripheral compartment and redistributed to the central compartment. In addition, Tr exhibited significant anti‐hyperglycemic and antihyperlipidemic efficacy against high‐fat diet‐induced streptozotocin‐induced type 2 diabetic rats.

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