Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery

Abstract

This study aims at formulating solid lipid nanoparticles (SLNs) of quercetin, a natural flavonoid with established antioxidant activity, for intravenous administration in order to improve its permeation across the blood-brain barrier into the CNS, and eventually to improve the therapeutic efficacy of this molecule in Alzheimer's disease. The SLNs of quercetin were formulated using Compritol as the lipid and Tween 80 as the surfactant through a microemulsification technique, and optimized employing a 3(2) central composite design (CCD). Selection of the optimized SLN formulation, using brute-force methodology and overlay plots, was based on its efficiency of entrapping quercetin inside the lipophilic core, particle size, surface charge potential and ability of the SLNs to release the entrapped drug completely. The optimized formulation was subjected to various in-vivo behavioral and biochemical studies in Wistar rats. The optimized formulation exhibited a particle size of less than 200 nm, 85.73% drug entrapment efficiency and a zeta potential of 21.05 mV. In all the in-vivo behavioral and biochemical experiments, the rats treated with SLN-encapsulated quercetin showed markedly better memory-retention vis-à-vis test and pure quercetin-treated rats. The studies demonstrated successful targeting of the potent natural antioxidant, quercetin, to brain as a novel strategy having significant therapeutic potential to treat Alzheimer's disease.