A reduction-degradable polymer prodrug for cisplatin delivery: Preparation, in vitro and in vivo evaluation.

We describe the development of novel reduction-sensitive therapeutic micelles consisting of polyethylene glycol-poly-(l-glutamic acid) (PEG-PLG), and conjugate with dithiodipropionic-Pt (IV) (DTDP-Pt). The drug delivery polymeric micelles lie in the covalent conjugation of each cisplatin drug to the PLG chains through a disulfide bond. The resulting micelles show well-controlled cisplatin loading yield, excellent reduction-responsive drug release kinetics, and enhanced in vitro cytotoxicity against cancer cells. The in vivo studies on the subcutaneous human ovarian carcinoma SKOV-3 xenograft model confirmed that PEG-P(LG-DTDP-Pt) micelles showed significant antitumor activity and reduced side effects, compared with free cisplatin. This characteristic drug release profile holds the promise to suppress cancer cell by rapidly releasing a high dose of chemotherapy drugs inside the tumor cells, thereby improving the therapeutic efficacy of the drug payload.