Alpha-mangostin-loaded PLGA Nanoparticles for Cholangiocarcinoma

Abstract

The present study aimed to formulate and characterize the AM-loaded PLGA nanoparticles (AM-PLGA-NPs) and further evaluated their antiproliferative and proapoptotic activities, including inhibitory activities on CCA cell invasion and migra-tion. Alpha-mangostin, a natural xanthone mainly extracted from the pericarp of Garcinia mangostana, has been shown to have promising anticancer properties in many types of cancer. PLGA MW 7,000-17,000 and 38,000-54,000 were used to make the AM-PLGA-NPs using the solvent displacement method. Physical (particle size and morphology, polydispersity index, and zeta potential) and pharmaceutical (encapsulation efficiency, loading efficiency, and drug release profile) parameters were assessed for the optimised AM-PLGA-NPs. . The morphology of the AM-PLGA-NPs and PLGA-NPs were examined under a transmission electron microscope (TEM). The MTT assay, flow-cytometry, QCM ECMatrix cell migration and cell invasion assays were used to evaluate antiproliferative and proapoptotic activities, including inhibitory activities on CCA cell (CL-6 and HuCCT-1) invasion and migration, respectively. The inhibitory activities of AM-PLGA-NPs on the migration and invasion of both CCA cell lines were concentration- and time-dependent, while no inhibitory effect was found with OUMS-36T-1F cells. AM-PLGA-NPs showed relatively potent and selective antiproliferative and proapoptotic activities in both CCA cell lines in a concentration- and time-dependent manner. Results revealed that PLGA nanoparticles could be a suitable nanocarrier to encapsulate AM for its delivery to CCA cells. The underlying molecular mechanisms of AM-PLGA-NPs involved in these activities should be further investigated.