Tailoring dexamethasone loaded albumin nanoparticles: A full factorial design with enhanced anti-inflammatory activity In vivo

Abstract

Protein-based nanoparticles (NPs) are biodegradable, biocompatible, and easily amenable to chemical modifications to allow for the incorporation of bioactive compounds. In the current study, we adopted a full factorial design to optimize dexamethasone disodium phosphate (Dex) encapsulation within NPs formed with bovine serum albumin (BSA) and stabilized using polyethylenimine (PEI). The optimized NP size (<200 nm dia.), zeta potential (−23.3 mV), and entrapment efficiency (67.4%) were occurred at 0.652 mg, 0.04, 5%, and 8.3 for solution concentration of Dex, PEI/BSA molar ratio, BSA solution concentration, and solution pH, respectively. Incorporation of Dex resulted in a decrease in alpha helix content of BSA indicating a change in its secondary structure. Dex loaded NPs yielded a bimodal release of Dex over an extended period of time via a quasi-Fickian diffusion mechanism. The in vivo anti-inflammatory activity of BSA/PEI Dex NPs surpassed that of free Dex in carrageenan-induced hind paw edema in rats as evidenced by enhanced suppression of oxidative stress, abrogation of NF-κB-p65 expression, as well as reduced myositis and inflammatory cell infiltration. The extended-release profile of BSA/PEI Dex NPs is crucial for achieving a significantly significant anti-inflammatory activity.