Design of experiment approach based formulation optimization of berberine loaded solid lipid nanoparticle for antihyperlipidemic activity

Abstract

Berberine is an isoquinoline alkaloid possesses multitude of biological effects. However, quaternary amine cation of berberine causes poor water solubility, resulting in low bioavailability which limits its pharmacological purpose. The aim of this study was to prepare and optimize berberine loaded solid lipid nanoparticle and to evaluate its pharmacokinetic and antihyperlipidemic activity. The solid lipid nanoparticles were prepared by solvent injection method and 32 full factorial design was used to study the effect of concentration of polyvinyl alcohol (X1) and amount of lipid (X2) on particle size (Y1) and entrapment efficiency (Y2). The formulation was optimized using desirability function and evaluated for physicochemical, morphological, in vitro drug release and in vivo pharmacokinetic study. In vivo antihyperlipidemic activity of the formulation was also studied using high fat diet induced hyperlipidemia model. The formulation optimized by validated experimental design comprise of 1 % w/v polyvinyl alcohol, 279 mg lipid (stearic acid) to achieve particle size of 395 nm with 82.44 % entrapment efficiency. In vitro release study of berberine loaded solid lipid nanoparticle showed an initial burst release followed by slow and continuous release. Berberine loaded solid lipid nanoparticle also showed 4.13 folds improvement in relative bioavailability compared to Berberine suspension. Furthermore, Berberine loaded solid lipid nanoparticle ameliorate the levels of total cholesterol (-41 %), TG (-49 %), lipoprotein cholesterol-C (-80 %) and high-density lipoprotein cholesterol(+119 %) compared to hyperlipidemic control and also found to be better than pure drug. The prepared berberine loaded solid lipid nanoparticle are successful drug delivery system demonstrating its effectiveness in controlling hyperlipidemia due to the improved bioavailability of berberine.