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Polyanhydride Doxorubicin Conjugate Particles as a Controlled Release Formulation for Chemotherapy

Nisarg J. Shah, Benjamin C. Tang, Jie Fu, and Justin S. Hanes. Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N Charles St, NEB 111, Baltimore, MD 21218

Drug polyanhydride conjugates improve therapy regimens as they have the advantage of maintaining drug concentration at target sites through sustained release while reducing toxic side effects and lowering dosage requirements. Here, we conjugate doxorubicin, a front line chemotherapeutic, to a poly(ethylene glycol) - poly(sebacic anhydride) (PEG:PSA) copolymer via an amide linkage to form micro and nano size particles capable of delivering doxorubicin. Particles released doxorubicin in vitro, and the drug retained cytotoxic activity. Electron micrographs and zeta potential measurements suggest a dense coating of PEG on the surface of the particles. These studies demonstrate that polymer-drug conjugate particles can be utilized for controlled and sustained release of front line chemotherapeutics.