Efficient nose-to-brain delivery of chitosan-coated resveratrol nanoemulsion in rats: Formulation optimized using D-optimal mixture design
Khushwant S. Yadav, Harsh P. Nijhawan, Prabhuti Nirale, Devansh Singhal, Govind Soni
Abstract
Resveratrol, a notable natural phytoconstituent with potent anti-inflammatory, anti-oxidant, anti-aging, and neuroprotective capabilities, holds promise for treating neurodegenerative diseases. However, its therapeutic potential is hindered by poor bioavailability due to extensive hepatic metabolism. To address this challenge, this study aimed to develop a chitosan-coated nanoemulsion to enhance the resveratrol delivery and brain targeting via the intranasal route, bypassing the first-pass metabolism. The coated nanoemulsion was formulated using resveratrol, oleic acid, tween 20, and transcutol P, with stability ensured through a ternary phase diagram. Optimization using the D-optimal mixture design yielded a nanoemulsion formulation with an average globule size of 50.9 ± 3.53 nm, while the chitosan-coated nanoemulsion measured 89.2 ± 2.68 nm. In-vitro studies showed drug release of 93.59 ± 2.89% in 24 h, whereas the chitosan-coated nanoemulsion extended the release to 96.72 ± 2.98% over 36 h. Ex-vivo studies further confirmed the enhanced permeability of the chitosan-coated nanoemulsion. In-vivo experiments demonstrated significantly higher brain concentration of resveratrol in rats when administered with chitosan-coated nanoemulsion via the intranasal route, compared to uncoated formulation and conventional solutions. The study’s findings highlight the potential of chitosan-coated nanoemulsion to overcome resveratrol’s bioavailability challenges, providing a promising approach for its applications in neurodegenerative diseases.