Systematically designed chitosan-coated solid lipid nanoparticles of ferulic acid for effective management of Alzheimer’s disease: A preclinical evidence

Abstract

Ferulic acid (FA) is a ubiquitous natural plant bioactive with distinctive promise in neurodegenerative disorders. However, its therapeutic efficacy gets compromised owing to its poor aqueous solubility, inadequate permeability across lipophilic barriers, and extensive first-pass metabolism. The current studies, therefore, were undertaken to systematically develop chitosan-coated solid lipid nanoparticles (SLNs) using QbD paradigms for improved efficacy of FA in the management of Alzheimer’s disease (AD). SLNs of FA were formulated employing Compritol as lipid and polysorbate 80 as surfactant and optimised using a 32 Central Composite Design (CCD). The optimized formulation, surface-coated with chitosan using ionic gelation, exhibited particle size of 185 nm, entrapment efficiency of 51.2 % and zeta potential of 12.4 mV. FTIR and DSC studies verified the compatibility of FA with formulation excipients, PXRD construed significant loss of drug crystallinity, while FESEM depicted existence of uniform spherical nanoparticles with little aggregation. Notable improvement in ex vivo mucoadhesion and permeation studies using goat nasal mucosa, coupled with extension in in vitro drug release, was obtained with SLNs. Substantial improvement with SLNs in cognitive ability through the reduction in escape latency time during behavioural studies, together with significant improvement in various biochemical parameters and body weight gain was observed in AD-induced rats. Histopathological images of different rat organs showed no perceptible change(s) in tissue morphology. Overall, these preclinical findings successfully demonstrate improved anti-AD efficacy, superior nasal mucoadhesion and permeation, extended drug release, improved patient compliance potential, safety and robustness of the developed lipidic nanoconstructs of FA through intranasal route.