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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Enhanced Bioavailability and Higher Uptake of Brain-Targeted Surface Engineered Delivery System of Naringenin developed as a Therapeutic for Autism Spectrum Disorder

Author(s): Ranjana Bhandari, Jyoti K Paliwal and Anurag Kuhad*

Volume 20, Issue 2, 2023

Published on: 05 July, 2022

Page: [158 - 182] Pages: 25

DOI: 10.2174/1567201819666220303101506

Price: $65

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Abstract

Background: Neuroinflammation resulting from oxidative and nitrosative stress is associated with various neurological disorders and involves the generation of pro-inflammatory cytokines and microglial activation. Dietary phytochemicals are safer and more valuable adjunct neurotherapeutic agents which can be added to the therapeutic regimen. These compounds provide neuroprotection by the modulation of various signaling pathways.

Introduction: Naringenin (NGN) is a phytochemical having low oral bioavailability because of poor solubility, and adding to this limitation is enhanced efflux by P-glycoprotein transporters in neuroinflammatory diseases.

Methods: Hence, as a solution for these limitations, naringenin encapsulated poly-lactic-co-glycolic acid (PLGA) nanocarriers were developed using the nanoprecipitation technique and coated with 1% glutathione (GSH) and 1% Tween 80 to enhance brain delivery.

Results: Coated and uncoated NGN-PLGA nanoparticles (NGN-PLGA-NPs) were spherical, monodispersed, stable, and non-toxic, with a particle size of less than 200 nm. They had negative zeta-potential values, 80% entrapment efficiency, and sustained drug release of 81.8% (uncoated), 80.13%, and 78.43% (coated) in 24 hours. FT-IR, DSC, PXRD, and NMR confirmed the drug encapsulation and coating over nanoparticles. In vivo brain uptake showed greater fluorescence intensity of the coated nanoparticles in the brain than uncoated nanoparticles. In addition, there was a 2.33-fold increase in bioavailability after coating compared to naringenin suspension and enhanced brain uptake.

Conclusion: Present studies indicate sustained and targeted brain delivery of naringenin via the ligandcoated delivery system by inhibiting enhanced P-glycoprotein (P-gp) efflux occurring in autism spectrum disorders due to neuroinflammation.

Keywords: Naringenin, poly-lactic-co-glycolic acid (PLGA), polymeric nanoparticles, glutathione (GSH), Tween 80, brain targeting.

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