Delivery of oseltamivir phosphate and gemcibatine from implantable poly (D,L-lactic-co-glycolic acid) cylinders for the treatment of pancreatic cancer
Drug delivery , Pancreatic cancer , Poly (D,L-lactic-co-glycolic acid) , Sustained release
The aim of the study was to develop implantable poly (D,L-lactic-co-glycolic acid) (PLGA) cylinders capable of releasing oseltamivir phosphate (OP) and gemcitabine (GEM) over 30 days and to establish proof of principle for the sustained delivery of OP and GEM for the treatment of pancreatic cancer. Resistance to the current standard of care, GEM, is common in pancreatic cancer. Recent studies have indicated mammalian neuraminidase 1 (Neu1) as a potential therapeutic target due to its role in receptor tyrosine kinase activation. OP inhibits Neu1 and has shown promise as a therapeutic agent for the treatment of pancreatic cancer. In vitro experiments have indicated combined treatment with OP and GEM may be more effective than either drug alone. Localized treatment with OP and GEM will allow a higher drug concentration at the tumor site while reducing systemic toxicity. OP and GEM were encapsulated in implantable PLGA single layered and double layered cylinders, which were capable of releasing OP and GEM over 30 days. Single layered cylinders were approximately 9 mm in length and 4 mm in diameter, while double layered cylinders were 10 mm by 5 mm. Double layered cylinders containing OP and GEM in distinct layers, termed OPin/GEMout and GEMin/OPout, displayed the most linear release of OP and GEM and were selected for cell viability testing. OP and GEM released from OPin/GEMout and GEMin/OPout cylinders effectively reduced cell viability of pancreatic cancer cell line PANC1 and GEM-resistant PANC1 (PANC1 GEMR) in experiments lasting 3, 6, 10, and 15 days. PLGA had no effect on cell viability. Future work should include in vivo studies with OPin/GEMout and GEMin/OPout cylinders in a murine model of pancreatic cancer.