期刊
MATERIALS
卷 14, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ma14174917
关键词
pancreatic cancer; nanoparticles; PLGA; nanocarriers; terpenoids; naturally derived compounds; ursolic acid
类别
资金
- Polish Ministry of Science and Higher Education for the Faculty of Biotechnology of the University of Wroclaw
Pancreatic Ductal Adenocarcinoma is one of the deadliest and hardest to treat types of cancer, with a critical need for new drugs and therapies. Natural compounds, such as ursolic acid, have shown high cytotoxic potential towards cancer cells, but their minimal water solubility requires the preparation of nanocarriers for delivery. Using PLGA polymeric nanocarriers can enhance the biological activity of ursolic acid and potentially provide effective therapies for PDAC.
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.
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