Wongrakpanich A.Bui Thi Thu H.Sakchaisri K.Taresco V.Crucitti V.C.Bunsupa S.Suksiriworapong J.Mahidol University2024-04-052024-04-052024-05-01Journal of Drug Delivery Science and Technology Vol.95 (2024)17732247https://repository.li.mahidol.ac.th/handle/123456789/97886This study explored the co-delivery of curcumin (CUR) and resveratrol (RV) using folic acid-conjugated poly(glycerol adipate)-based nanoparticles (FPPC NPs) to enhance their synergistic anticancer effects against osteosarcoma. Based on synergistic toxicity experiments against Saos-2 cells, the optimal synergistic CUR:RV ratios were 1:2 and 1:3, which were used for co-encapsulation. Increasing the amount of RV in the co-loaded NPs did not affect the properties of the nanocarriers, but predominantly increased the loading capacity of RV, especially at the 1:3 ratio, by 1.8–2.0 times, mediated by their interaction. All co-loaded NPs demonstrated sustained release of CUR with a burst release of RV, and the presence of RV accelerated the initial release of CUR from the carriers. Furthermore, the co-encapsulated NPs maintained CUR and RV synergism and greatly enhanced their toxicity against osteosarcoma by at least 1.8 times compared to their corresponding solutions through profound accumulation of Saos-2 cells in the sub G1 phase and late apoptosis. The internalization of FPPC NPs into cells via endocytosis was dose- and time-dependent. This study offers a proof-of-concept for a potential co-delivery system using tumor-targeted poly(glycerol adipate)-based NPs to enhance the anticancer activity of CUR and RV against osteosarcoma.Pharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/j.jddst.2024.1056102-s2.0-85189043357