Novel chitosan-based solid-lipid nanoparticles to enhance the bio-residence of the miraculous phytochemical "Apocynin"

Abstract

Apocynin (APO), a specific NADPH oxidase inhibitor, is a bioactive phytochemical that exhibits versatile pharmacological activities. However, its rapid elimination and poor bioavailability represent great challenges to pharmaceutical scientists. Accordingly, novel chitosan-based APO-loaded solid lipid nanoparticles (CS,APO - loaded SLN_S) were developed to address such obstacles. A full 2⁴ factorial design of experiment approach was employed to evaluate the individual and combined effect of critical process parameters namely; the amount of glycerol tristearate (GTS, X_A) and sucrose mono palmitate (SMP, X_B) as well as the concentration of chitosan (CS, X_C) and polyvinyl alcohol (PVA, X_D), on different critical quality attributes. Full characterization and extensive in vitro-in vivo evaluations of the optimized SLNs formula were conducted. The optimized formula, with core (CS,APO) and shell (PVA), has enhanced oral and intravenous bioavailability in rats as clearly verified when compared with APO solution. Probably, PVA hindered opsonization intravenously and SLNs reduced pre-systemic effect. In conclusion, the novel chitosan-based SLNs system would open new vistas in potentiating the bioavailability and sustaining the effect of APO and other bioactive phytochemicals with comparable properties.

Keywords: Apocynin; Bioactive phytochemical; Bioavailability; Chitosan; Factorial design; Solid lipid nanoparticles.