Delivery of oseltamivir phosphate and gemcibatine from implantable poly (D,L-lactic-co-glycolic acid) cylinders for the treatment of pancreatic cancer
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Authors
Allison, Stephanie
Date
2015-09-08
Type
thesis
Language
eng
Keyword
Drug delivery , Pancreatic cancer , Poly (D,L-lactic-co-glycolic acid) , Sustained release
Alternative Title
Abstract
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.
Description
Thesis (Master, Chemical Engineering) -- Queen's University, 2015-08-28 14:17:15.912
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.