Enhanced bioactivity and oral bioavailability of α-mangostin through formulation in biodegradable nanoparticles

Abstract Purpose: Despite the promising therapeutic potential of α-mangostin (MG) as a nutraceutical anticancer agent, its clinical utility remains limited due to poor oral bioavailability. This study aimed to enhance the bioavailability and anticancer activity of MG through formulation into biodegradable polymeric nanoparticles. Methods: MG-loaded nanoparticles (MG-NPs) were prepared using polylactic-co-glycolic acid (PLGA) as the carrier polymer via the emulsion-evaporation method. The prepared nanoparticles were characterized for particle size, zeta potential, morphology (AFM), chemical compatibility (FTIR), thermal behavior (DSC), and crystallinity (XRD). Drug loading, entrapment efficiency, and in vitro release profiles were evaluated. Cytotoxicity assays were conducted on Caco-2, HepG2, and MCF-7 cell lines. Furthermore, in vivo oral absorption studies were performed in Balb/c mice to compare the bioavailability of MG-NPs with free MG. Results: The MG-NPs exhibited uniform spherical morphology with nano-size distribution and high entrapment and loading efficiencies. The release profile showed a diffusion-controlled release mechanism. Cytotoxicity assays revealed significantly enhanced antiproliferative effects of MG-NPs on all tested cell lines compared to free MG. In vivo pharmacokinetic analysis demonstrated a 1.75-fold increase in area under the curve (AUC) for MG-NPs versus free MG, indicating improved oral absorption. Conclusion: Formulating α-mangostin as PLGA-based biodegradable nanoparticles successfully improved its oral bioavailability and anticancer efficacy. This approach provides a promising strategy for enhancing the clinical applicability of MG as a therapeutic agent.