FORMULATION DEVELOPMENT OF CELASTROL POLYMERIC NANOPARTICLES AS A NANO-THERAPEUTIC APPROACH FOR RHEUMATOID ARTHRITIS

Abstract

Celastrol is a bioactive pentacyclic triterpenoid with potent anti-inflammatory activity, but its pharmaceutical development is restricted by extremely poor aqueous solubility, limited bioavailability, rapid systemic elimination, and concentration-dependent toxicity. The present study aimed to develop and optimize Celastrol-loaded PEGylated PLGA nanoparticles for improved in vitro anti-inflammatory performance relevant to rheumatoid arthritis. Nanoparticles were prepared by nanoprecipitation using PLGA and mPEG-PLGA at a fixed 80:20 w/w ratio and optimized through a three-factor, three-level Box–Behnken Design. Total polymer concentration, Poloxamer 188 concentration, and Celastrol-to-total-polymer ratio were evaluated against particle size, entrapment efficiency, and drug release at 24 h. The optimized formulation exhibited a mean particle size of 150.6 ± 3.4 nm, PDI of 0.186 ± 0.012, zeta potential of −24.8 ± 1.7 mV, entrapment efficiency of 87.1 ± 1.5%, and sustained drug release of 93.1 ± 1.3% over 48 h. FTIR, DSC, PXRD, and TEM analyses confirmed drug–polymer compatibility, reduced Celastrol crystallinity, and spherical nanoparticle morphology. In LPS-stimulated RAW 264.7 macrophages, Celastrol nanoparticles showed improved cellular tolerability and significantly reduced intracellular reactive oxygen species, nitric oxide production, and secretion of TNF-α, IL-6, and IL-1β compared with free Celastrol. The formulation remained physically stable during three months of storage. These findings demonstrate that PEGylated PLGA nanoparticles can improve the pharmaceutical performance and in vitro anti-inflammatory activity of Celastrol and warrant further investigation in rheumatoid arthritis models.