Polymer-drug conjugation of small molecule chemotherapeutics to highly water-soluble and biocompatible polymers, such as poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC), imparts excellent aqueous solubility, improved pharmacokinetics, and reduced off-target toxicity to those drugs, allowing for an enhancement of antitumor efficacy. A novel polyMPC-based system incorporating temozolomide (TMZ) was developed for the treatment of glioblastoma, a highly aggressive and infiltrative brain cancer. Using a versatile TMZ-methacrylate, well-defined and water-soluble polyMPC-TMZ random and block copolymers were prepared by controlled free radical polymerization over a wide range of drug incorporations (15-50 mole percent TMZ). The aqueous solution assembly properties of the conjugates were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), showing the formation of nanoscale aggregates of the block copolymers. The polyMPC-TMZ copolymers exhibited enhanced solution stability of pendent TMZ moieties in physiological conditions, as demonstrated by UV-vis spectroscopy. Furthermore, polyMPC-TMZ conjugates showed architecture- and drug loading-dependent cytotoxicity in both chemosensitive and chemoresistant glioblastoma cell lines. This polyMPC-TMZ system represents a versatile application of the polyMPC-based prodrug platform which holds promise for future <i>in vivo</i> evaluations.

Polymer zwitterion-temozolomide conjugates for glioblastoma treatment

2019 Spring National Meeting

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