Optimization of Curcuminoid-Loaded PLGA Nanoparticles Using Box-Behnken Statistical Design

Abstract

Curcuminoids are a mixture of phenolic compounds isolated from Curcuma longa L. (turmeric) rhizomes that possess antioxidant, anti-inflammatory, anti-Alzheimer and anticancer activities. However, curcuminoids have poor solubility in acid and neutral solutions, rapid decomposition in neutral and alkaline solutions, and low bioavailability that limits their use as therapeutic agents. To overcome these problems, statistical design for preparation and characterization of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles as a carrier for curcuminoids was evaluated in this study. The curcuminoid-loaded PLGA nanoparticles were prepared by a modified spontaneous emulsification solvent diffusion method using polyvinyl alcohol (PVA) as a stabilizer. The formulations were optimized using three-factor, three-level Box-Behnken experimental design. The independent variables in the formulations were the lactide/glycolide (LA/GA) molar ratio of PLGA (50:50 to 85:15), the curcuminoid concentration (2%-10%, w/v), and the PVA concentration (3%-7%, w/v). The dependent variables were particle size, loading capacity and entrapment efficiency. Statistical evaluation showed that the LA/GA molar ratio of PLGA and the curcuminoid and PVA concentrations all affected the characteristics of the PLGA nanoparticles. To achieve a minimum particle size and maximum loading capacity and entrapment efficiency, the optimal formulation of the curcuminoid-loaded PLGA nanoparticles had a LA/GA molar ratio of PLGA of 50:50, 10% (w/v) curcuminoids, and 3% (w/v) PVA. A sustainable in vitro release profile of curcuminoids was obtained from this optimal formulation.