Synthesis, characterization, and in vivo evaluation of poly(ethylene oxide-co-glycidol)-platinate conjugate

Abstract

Poly(ethylene oxide-co-glycidol) (poly(EO-co-Gly)), a member of polyether polyol (PEP), resembles polyethylene glycol (PEG) in the polymer backbone but distinguishes itself by having multiple pendent groups along the main chain. We showed that this new bioconjugation material is biocompatible by its lack of toxicity on fibroblast cell growth, inactivity in hemolysis, and the absence of side effects after injection in mice. The usefulness of poly(EO-co-Gly) as a polymeric drug carrier was demonstrated via the preparation and characterization of a new anticancer polymer-drug conjugate, poly(EO-co-Gly)-platinate. The drug loading was 9.1-12.6% (cisplatin/conjugate w/w), at least four times higher than a PEG conjugate of similar molecular weight. The aqueous solubility of cisplatin was increased by around 10 folds after conjugation. Platinum complexes were released from the conjugate in a sustained manner over 2 days. The release of active drugs was confirmed by the antitumor activity of poly(EO-co-Gly)-platinate in vitro against HONE-1 (human nasopharyngeal carcinoma) and MCF-7 (human breast cancer), albeit at a potency lower than free cisplatin. Poly(EO-co-Gly)-platinate improved the therapeutic index of cisplatin in vivo. The conjugate had a similar antitumor activity as free cisplatin in nude mice bearing HONE-1 xenografts, and achieved 52% inhibition of tumor growth at the conclusion of the study. While free cisplatin injection caused a severe loss in body weight (>20%), poly(EO-co-Gly)-platinate resulted in mild side effects. These findings support that poly(EO-co-Gly) is a suitable drug carrier.