title: Drug release mechanism of paclitaxel from a chitosan-lipid implant system: effect of swelling, degradation and morphology.
abstract: Localized and sustained delivery of anti-cancer agents to the tumor site has great potential for the treatment of solid tumors. A chitosan-egg phosphatidylcholine (chitosan-ePC) implant system containing PLA-b-PEG/PLA nanoparticles has been developed for the delivery of paclitaxel to treat ovarian cancer. Production of volumes of ascites fluid in the peritoneal cavity is a physical manifestation of ovarian cancer. In vitro release studies of paclitaxel from the implant were conducted in various fluids including human ascites fluid. A strong correlation (r2=0.977) was found between the release of paclitaxel in ascites fluid and PBS containing lysozyme (pH 7.4) at 37 degrees C. The drug release mechanism for this system was proposed based on swelling, degradation and morphology data. In addition, in vitro release of paclitaxel was found to be a good indicator of the in vivo release profile (correlation between release rates: r2=0.965). Release of paclitaxel was found to be sustained over a four-week period following implantation of the chitosan-ePC system into the peritoneal cavity of healthy Balb/C mice. Also, the concentrations of paclitaxel in both plasma and tissues (e.g. liver, kidney and small intestine) were found to be relatively constant.
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, ON Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lim Soo
authors.forename: Jaepyoung
authors.initials: J
authors.lastname: Cho
authors.forename: Justin
authors.initials: J
authors.lastname: Grant
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ho
authors.forename: Micheline
authors.initials: M
authors.lastname: Piquette-Miller
authors.forename: Christine
authors.initials: C
authors.lastname: Allen
mesh_terms: D000818:Animals; D001201:Ascites / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D004343:Drug Implants / Q000737:chemistry*; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage*; D019736:Prostheses and Implants
chemical_list: D004343:Drug Implants; D008055:Lipids; D048271:Chitosan; D017239:Paclitaxel