In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis

摘要: Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis intra-abdominal cancers, occurring in as many 50% colon cancer patients, and associated with poor prognosis. For the treatment CRPC, cytoreductive surgery alone inadequate at microscopic level, chemotherapy has limited effect due to peritoneal-plasma barrier. Intraperitoneal logically proposed early after treat residual small tumors. Traditional typically infused intravenously. However, intraperitoneal allows direct contact anti-cancer agents tumor cells, which could improve regression efficacy minimize toxicity. Furthermore, injectable thermosensitive polymer hydrogels have shown promising applications controlled drug delivery systems for situ chemotherapy. In this study, biodegradable thermogelling block copolymer poly(L-lactide acid)–Pluronic L35–poly(L-lactide acid) (PLLA–L35–PLLA) was synthesized fabricate novel local system (DOC-M/OXA-H) composed docetaxel loaded micelles (DOC-M) an oxaliplatin hydrogel (OXA-H). DOC, widely used anticancer extremely high hydrophobicity, into by membrane dialysis method without using any surfactants or excipients. And DOC-M encapsulated OXA-H achieve aim synergistic combination therapy significantly good patient compliance. As result, DOC-M/OXA-H flowing sol ambient temperature became solid-like gel physiological crosslinking agent. Meanwhile, demonstrated slow sustained release profile DOC OXA exhibited quite potent cytotoxicity vitro. vivo antitumor test CRPC-bearing mice suggested that more competent suppressing growth prolonging survival time inhibiting cell proliferation angiogenesis increasing apoptosis cells. Overall, our data may be potentially useful CRPC.