Abstract 4770: Delivery of doxorubicin to multi-drug resistant murine xenografts via drug-loaded micelles formed from mixtures of amphiphilic triblock copolymers

BACKGROUND: The toxicity of chemotherapeutic drugs is often the limiting factor in patient dosing and can be the source of severe discomfort and suffering for patients undergoing chemotherapy. For example, the anthracycline antibiotic doxorubicin (DOX) is a potent chemotherapeutic but prolonged use can also lead to permanent heart damage. Tumors can also develop resistance to DOX by increased expression of drug efflux pumps. Nanoparticle formulations of DOX have been reported to improve tumor-specific delivery via the enhanced permeability and retention (EPR) effect. METHODS: In this work, we have encapsulated DOX in polymeric micelles formed from mixtures of amphiphilic triblock copolymers. The copolymers are composed of a hydrophobic polymer segment flanked by two hydrophilic blocks. Two different copolymers were used to form the mixed micelles: a copolymer of poly(ethylene oxide) and poly(hydroxybutyrate) (PEO-PHB-PEO), and a copolymer of poly(ethylene oxide) and poly(propylene oxide) (Pluronic F127). We hypothesize that forming mixed micelles will improve drug loading and enable preparation at room temperature (where Pluronic F127 micelles are highly unstable), while facilitating drug delivery by utilizing the stability of Pluronic F127 micelles at physiological temperatures. RESULTS: We have demonstrated that the micelles formed from the mixtures of PEO-PHB-PEO and Pluronic F127 triblock copolymers provide a combination of high drug loading content and drug delivery capabilities. DOX loading for mixed micelles was greater than that for Pluronic F127-only micelles (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4770. doi:1538-7445.AM2012-4770