Characterization of polyglutamic acid-composite nanoparticles for controlled release of anti-cancer drugs

Dr. Argyrios Margaritis, Department of Chemical and Biochemical Engineering, University of Western Ontario


21 October 2010 at 10:30

Location: JHE 326H

Conventional chemotherapy involves the use of anti-cancer drugs via intra-venous injection which reaches both cancer and healthy cells. The main disadvantages of this method include: short half-life of drug in the blood, small amounts reach the targeted cancer cells, high cost and severe side-effects to the patients. Recent advances in nanotechnology involve the development of drug-loaded nanoparticles which are used to deliver anti-cancer drugs to specific cancer cells under controlled release conditions. Different biocompatible, non-toxic polymers are used to produce the nanoparticles for cancer chemotherapy. This has drawn the world-wide attention of researchers and biopharmaceutical companies using animal models.
In this work we present results on the use of Gamma-Polyglutamic Acid (PGA) biopolymer to produce nanoparticles and encapsulate the anti-cancer drug Doxorubicin (DOX). Microbially produced PGA is used alone and in combination with Chitosan (CS) to form DOX-loaded nanoparticles at different conditions. The main mechanism of nanoparticle formation is the ionic complexation between PGA, DOX and CS. The size distribution, surface charge and diffusivity characteristics of PGA-DOX-CS nanoparticles were studied under the following variable conditions: order and time of mixing, mass ratios of PGA:DOX:CS, structure and molecular weight of components, and pH of solution. Rates of biodegradation of nanoparticles and rate of DOX release were studied as a function of time. Preliminary in-vitro cytotoxicity results are also reported using different size nanoparticles to kill human cancer cells HN-5a derived from Human gingival quamous carcinoma.


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