Preparation of pH-sensitive, polymeric prodrug micelles for delivery and controlled release of cisplatin

*E-mail: sjt.rezaei@znu.ac.ir Cancer, as a leading cause of death worldwide, has gained much attention in recent decades [1]. Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge [2]. Cis-diaminedichloroplatinum(II) (cisplatin, CDDP) is one of the oldest chemotherapy drugs available and has been in widespread use to treat a wide range of solid tumors including ovarian, cervical, head and neck, and non-small-cell lung cancer. Treatment is usually limited, however, by side-effects such as nephrotoxicity, emetogenesis, and neurotoxicity. One of the most promising strategies to enhance targeting is to employ polymeric nanocarriers (PNs) to achieve passive targeting via the enhanced permeation retention effect (EPR) and protection of cisplatin from undesirable binding events during drug distribution in the body, while facilitating the transport of the drug across the cell membrane via endocytosis at the site of action [3-4]. In this work, we were designed a novel pH-sensitive nontoxic polymeric micelles based on biocompatible polymers such as polyethylene glycol (PEG) and glycidyl azide polymer (GAP). To assess the suitability of prepared copolymer as a drug carrier, drug loading and in vitro release studies are performed using cisplatin. We extensively examined the drug loading capacities, in vitro pH dependent releasing profile and physicochemical characteristics of the self-assembled block copolymer micelles.