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Versatile Synthesis of Polymer-Temozolomide Conjugates
Matthew Skinner1, Sarah M Ward1, Todd Emrick1
1Polymer Science and Engineering Department, University of Massachusetts, 120 Governors Drive, Amherst, Massachusetts 01003, United States.
Abstract:
A new and versatile synthesis was developed to produce polymer prodrugs composed of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC) conjugated covalently to the glioblastoma drug Temozolomide (TMZ). Through a controlled free radical copolymerization of a TMZ-substituted methacrylate and MPC, water-soluble polyMPC-TMZ conjugates were realized with TMZ loadings of >50 mol %. After polymerization, the structural fidelity of the pendent TMZ moieties was confirmed by NMR and UV-vis spectroscopy, while molecular weight estimation by gel permeation chromatography (GPC) confirmed the desired control over the polymerization, with isolated polymer-TMZ conjugates exhibiting narrow molecular weight distributions. This synthetic design opens new possibilities for formulating numerous types of polymeric TMZ-based structures that are of interest for treating glioblastoma.
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