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
Michael Hrynyk, Jordon P Ellis, Fiona Haxho, Stephanie Allison, Joseph AM Steele, Samar Abdulkhalek, Ronald J Neufeld, Myron R Szewczuk
Drug Design, Development and Therapy | DOVE MEDICAL PRESS LTD | Published : 2015
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..View full abstract
This work was supported in part by grants to MR Szewczuk and RJ Neufeld from the Natural Sciences and Engineering Research Council of Canada and private sector cancer funding from the Josefowitz Family to MR Szewczuk. The cancer contents of this report are covered by a PCT international patent application number, PCT/CA2011/050690. We thank Lacey Brodhagen and Alexandra Morris, Veterinarian Technologists for their veterinarian expertise and assistance with the animal work.