Development and In Vitro Characterization of Gemcitabine Loaded Nanoparticles for Pancreatic Cancer Therapy




Pham, Jennifer H.


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Pancreatic Ductal Adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths worldwide and the most common type of pancreatic malignancy (90%). With a poor five-year survival rate of only 5-8%, complete surgical resection remains the only curative treatment. However, most patients are diagnosed at a later stage where chemotherapy and radiotherapy are the only options. Gemcitabine is the FDA-approved treatment for PDAC, but the current therapy leads to more severe side effects due to the instability of gemcitabine in the blood stream and its poor membrane permeability. Nanoparticles are effective in cancer therapy because they allow modifications that make for a more effective delivery method and also reduces the toxicity to normal tissue. In this proposed study, we aim to formulate, optimize and evaluate the in vitro effectiveness of gemcitabine loaded nanoparticles in a PDAC cell line in order to improve the effectiveness of current chemotherapy treatments for pancreatic ductal adenocarcinoma. We found out of the three types of nanoplatforms used for encapsulating gemcitabine (GEM-NPs): polymeric, liposomal and lipid polymer hybrid, the liposomal nanoparticles were the most effective in the encapsulation of gemcitabine according to the physicochemical properties, such as average particle size, zeta potential, drug loading and encapsulation efficiency. In vitro functional evaluation of liposomal formulation was done in a PDAC cell line (PANC-1). This study suggests that the use of liposomal nanoparticles is the most beneficial in the encapsulation and delivery of gemcitabine.