Solid lipid nanoparticles for nose to brain delivery of donepezil: formulation, optimization by Box–Behnken design, in vitro and in vivo evaluation

摘要

This study was aimed at preparing and characterizing solid lipid nanoparticles (SLNs) of donepezil (DPL) for delivery to brain via nasal route. SLNs were prepared by solvent emulsification diffusion technique using glyceryl monostearate (GMS) as lipid and blend of tween 80 and poloxamer 188 (1:1) as surfactant. Box–Behnken design was applied for optimization by using drug to lipid ratio, surfactant concentration and stirring time as dependent variables and their effect were observed on particles size, entrapment efficiency and drug loading. Optimized formulation was evaluated for particle size, zeta potential, entrapment efficiency, drug loading, morphological analysis, crystallinity, in vitro drug release, in vivo (biodistribution, pharmacokinetic and Gama scintigraphy) studies. For optimized formulation (OD3), value of particle size, zeta potential, percent in vitro release, entrapment efficiency and drug loading was found to be 121.0?nm, –24.1?mV, 89.35%, 67.95% and 12.15%, respectively. Pharmacokinetic and biodistribution studies were performed on albino Wistar rats and value of AUC0–∞ in brain for DPL-SLNs i.n. was found to be nearly 2.61 times higher than that of DPL-Sol i.v., whereas 2.26 times superior than DPL-Sol administered intranasally. The scintigraphy images were taken in rabbit and result revealed the localization of drug in brain.