Back to Journals » Drug Design, Development and Therapy » Volume 9

Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma

Authors Hrynyk M, Ellis JP, Haxho F, Allison S, Steele JA, Abdulkhalek S, Neufeld RJ, Szewczuk M

Received 9 June 2015

Accepted for publication 2 July 2015

Published 10 August 2015 Volume 2015:9 Pages 4573—4586

DOI https://doi.org/10.2147/DDDT.S90170

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rekha Dhanwani

Peer reviewer comments 3

Editor who approved publication: Professor Shu-Feng Zhou


Michael Hrynyk,1 Jordon P Ellis,1 Fiona Haxho,2 Stephanie Allison,1 Joseph AM Steele,1 Samar Abdulkhalek,2 Ronald J Neufeld,1 Myron R Szewczuk2

1Department of Chemical Engineering, 2Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

Abstract: Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Here, the controlled release of OP from a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated for its role in limiting tumor neovascularization, growth, and metastasis. PLGA-OP cylinders over 30 days in vitro indicated 20%–25% release profiles within 48 hours followed by a continuous metronomic low dose release of 30%–50% OP for an additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31+ endothelial cells compared with the untreated cohort. These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer.

Keywords: pancreatic cancer, oseltamivir phosphate, PLGA, tumor neovascularization, metastasis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]