Abstract 5404: C6-ceramide containing anionic nanoliposomes are effective chemotherapy delivery vehicles for pancreatic cancer

Pancreatic ductal adenocarcinomas (PDACs) are highly fibrotic and poorly vascularized tumors, making systemic delivery of standard chemotherapies ineffective. To overcome the obstacles to delivering therapeutics to PDAC tumors, we have devised an innovative, biocompatible nanocarrier formulation that can deliver chemotherapeutic drugs to pancreatic cancer cells: pegylated anionic nanoliposomes (anionic NLs). By dynamic light scattering, anionic NLs are 85-90 nm in diameter and have a zeta potential of -20 mV. Compared to the more commonly used neutral NLs, the empty (unloaded) anionic NL formulation did not alter proliferation of either normal pancreatic epithelial cells (HPDEs) or PDAC cells. A variety of chemotherapeutic agents were then tested for their ability to be effectively encapsulated into anionic NLs via a temperature-dependent trapping mechanism. The chemotherapeutic drugs vincristine, vinblastine and 5-fluorouracil (5FU) were all effectively encapsulated into the anionic NL formulation, and anionic NLs encapsulated 5FU at reproducible concentrations of 3-4 mM. At 48 hours after a single dose of anionic NL-encapsulated 5FU, in vitro proliferation of pancreatic cancer cells was significantly reduced compared to unloaded NLs or to vehicle controls (p Citation Format: Christopher McGovern, Sriram Shanmugavelandy, Sara Shimko, Samuel Linton, Jenny Dai, Mark Kester, Jill P. Smith, Gail L. Matters. C6-ceramide containing anionic nanoliposomes are effective chemotherapy delivery vehicles for pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5404. doi:10.1158/1538-7445.AM2014-5404