In situ administration of temperature-sensitive hydrogel composite loading paclitaxel microspheres and cisplatin for the treatment of melanoma
Yanlin Liu, Wenqiong Ma, Ping Zhou, Qian Wen, Qinglian Wen, Yun Lu, Ling Zhao, Huan Shi, Jie Dai, Jianmei Li, Shaozhi Fu
Abstract
Chemotherapy is one of the main therapeutic strategies for the treatment of malignant melanoma. Conventional chemotherapeutic agents often lack targeting abilities, and efficacy is hampered by their high toxic effects to normal tissues and rapid clearance from the circulation. In this study, porous paclitaxel (PTX)-loaded polylactide (PLA) microspheres (PPMSs) were prepared by a modified double-emulsion-solvent evaporation method. In addition, PPMSs and cisplatin (DDP) were co-embedded in a thermosensitive hydrogel to construct a dual-drug co-delivery hydrogel system (PPMSs/DDP@Gel) for in-situ chemotherapy to treat melanoma by means of an intra-tumoral injection. The system allows for the sustained release of two drugs and exhibits good temperature-sensitive properties. In vitro antitumor activity showed that this hydrogel composite can induce B16 cell apoptosis and inhibit its migration. In vivo, anti-tumor studies have shown that the PPMSs/DDP@Gel significantly inhibited tumor growth, prolonged the survival of tumor-bearing mice, and had no obvious toxic side effects on major organs. Furthermore, immunohistochemical analysis revealed that PPMSs/DDP@Gel significantly inhibited tumor cell proliferation and promoted apoptosis of tumor cells. Taken together, the injectable temperature-sensitive PPMSs/DDP@Gel is a promising candidate for the local treatment of melanoma.