Optimization and Pharmacokinetic Study of Boswellic Acid–Loaded Chitosan-Guggul Gum Nanoparticles Using Box-Behnken Experimental Design

Abstract

Macromolecules are important in polymer-based drug delivery systems as they help in specific targeting. This study explores the use of guggul gum (GG) and chitosan (Ch) in encapsulating boswellic acid (BA) which has high first-pass metabolism and low aqueous solubility for possible uses in inflammatory conditions. Ionic complexation was used for nanoparticle formulation. The contents of guggul gum, chitosan, and boswellic acid were taken as independent variables, and their influence on encapsulation, particle size, and polydispersity were optimized by using Box-Behnken design. The developed formulation was assessed for drug release (in vitro) and release kinetics, stability, and preclinical pharmacokinetics. The formulation was also evaluated for inhibition of carrageenan-induced hind paw inflammation in rats. The nanoparticles were successfully prepared by ionic complexation method. The runs suggested by the design yielded a quadratic model for predicting the relationship between independent variables and responses. The optimum condition suggested by point prediction tool yielded spherical nanoparticles with 81.7% encapsulation, drug loading 21.2%, 377.19 nm size, and 0.201 PDI. The nanoparticles showed zero-order kinetics demonstrating an amalgamation of drug diffusion through matrix and erosion of polymeric medium. Ionic complexation is a suitable method for nanopartile formulation. GG-Ch nanoparticles are beneficial for specific delivery and anti-inflammation of boswellic acid. The bioavailability of boswellic acid was increased by 11.38 times when given as a GG-Ch nanoparticle. The nanoparticles were stable at 25 °C for 6 months.