Development and Characterization of Chitosan Nanoparticles Containing Quercetin-β-Cyclodextrin Inclusion Complex for Improved Solubility, Brain Targeting, and Neuroprotective Potential Against Epilepsy
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Abstract
The present study focuses on developing and optimising chitosan nanoparticles containing quercetin-β-cyclodextrin inclusion complex (QNPs) using the nanoprecipitation method to enhance quercetin's solubility, stability, and bioavailability. A comprehensive optimization study revealed that Batch B6, which utilized ethanol as the solvent, poloxamer 188 as the stabilizer, and chitosan at a concentration of 0.2% (w/v), exhibits optimal characteristics required for providing a stable colloidal system. The prepared nanoparticles were characterized for their physicochemical properties using FTIR, DSC, X-ray Diffraction, and SEM, which confirmed the successful inclusion of quercetin within the β-cyclodextrin complex and the reduction in crystallinity. In-vitro drug release studies demonstrated a controlled release profile for QNPs compared to free quercetin and the inclusion complex. Pharmacokinetic evaluation in mice via oral administration revealed a significant enhancement in systemic circulation and brain uptake, with QNPs showing a peak plasma concentration of 6.5 µg/mL at 2 h and a brain concentration of 3.5 µg/g at 4 h, indicating improved bioavailability and prolonged retention. In the Pentylenetetrazole and Kainic acid-induced epilepsy mice model, QNP significantly reduced seizure duration, frequency of seizures, and severity scores favoured the QNP formulation over free quercetin. QNPs also exhibited a significant neuroprotective effect by enhancing antioxidant enzyme levels such as superoxide dismutase, catalase, and glutathione reductase in brain tissue. Furthermore, Na⁺/K⁺-ATPase activity was significantly preserved in QNP-treated groups, indicating membrane stability and reduced neuronal excitability. These findings suggest that QNPs offer a promising strategy for enhancing quercetin's therapeutic efficacy in neurological disorders such as epilepsy.
期刊介绍：
AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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