title: Use of 5-Fluorouracil Loaded Micelles and Cisplatin in Thermosensitive Chitosan Hydrogel as an Efficient Therapy against Colorectal Peritoneal Carcinomatosis.
abstract: Colorectal peritoneal carcinomatosis (CRPC) is a common systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy against CRPC is at present the preferred treatment. The aim of this study is to develop a novel hydrogel drug delivery system through the combination of 5-fluorouracil (5-FU) loaded polymeric micelles and cisplatin (DDP) in biodegradable thermosensitive chitosan (CS) hydrogel. The prepared CS hydrogel drug is a free-flowing solution at room temperature and forms a stationary gel at body temperature. Therefore, a CRPC mouse model is established to investigate the antitumor activity of CS hydrogel drug system. The results suggest that intraperitoneal administration of CS hydrogel drug can inhibit tumor growth and metastasis, and prolong survival time compared with other groups, thus improving the chemotherapeutic effect. Ki-67 immunohistochemical analysis reveals that tumors in the CS hydrogel drug group has lower cell proliferation in contrast to other groups (P < 0.001). Furthermore, hematoxylin-eosin staining of liver and lung tissue indicates that the CS hydrogel drug has also a certain inhibitory effect on colorectal cancer metastasis to the liver and lung. Hence, the work highlights the potential clinical applications of the CS hydrogel drug.
authors.affiliation: Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yun
authors.affiliation: Department of Neurosurgery, the Affiliated 363 Hospital of Southwest Medical University, Chengdu, 610041, China.
authors.forename: Si Song
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Jin Ping
authors.initials: JP
authors.lastname: Yang
authors.affiliation: Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Ling Lin
authors.initials: LL
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Shao Zhi
authors.initials: SZ
authors.lastname: Fu
authors.affiliation: Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
authors.forename: Jing Bo
authors.initials: JB
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D065546:Drug Liberation; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007150:Immunohistochemistry; D007267:Injections; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008807:Mice, Inbred BALB C; D008823:Micelles; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012212:Rheology / Q000187:drug effects; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D008823:Micelles; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-fluorouracil; chitosan; cisplatin; colorectal peritoneal carcinomatosis; thermosensitive hydrogel