Evaluation Of The In Vitro Cytotoxic Activity Of Ursolic Acid Plga Nanoparticles Against Pancreatic Ductal Adenocarcinoma Cell Lines

Among all the types of cancer, Pancreatic Ductal Adenocarcinoma remains one of the deadliest and hardest to fight and there is a critical unmet need for new drugs and therapies for its treatment. Naturally derived compounds, such as pentacyclic triterpenoids, have gathered attention because of their high cytotoxic potential towards pancreatic cancer cells, with a wide biological activity spectrum, with ursolic acid (UA) being one of the most interesting. However, due to its minimal water solubility, it is necessary to prepare a nanocarrier vehicle to aid in the delivery of this compound. Poly(lactic-co-glycolic acid) or PLGA polymeric nanocarriers are an essential tool for ursolic acid delivery and can overcome the lack in its biological activity observed after incorporating within liposomes. We prepared UA-PLGA nanoparticles with a PEG modification, to achieve a long circulation time, by using a nanoprecipitation method and subsequently performed an MTT cytotoxicity assay towards AsPC-1 and BxPC-3 cells, with TEM visualization of the nanoparticles and their cellular uptake. We established repeatable preparation procedures of the nanoparticles and achieved biologically active nanocarriers with an IC50 below 30 mu M, with an appropriate size for intravenous dosage (around 140 nm), high sample homogeneity (below 0.2) and reasonable encapsulation efficiency (up to 50%). These results represent the first steps in the development of potentially effective PDAC therapies based on novel biologically active and promising triterpenoids.