title: Thermosensitive hydrogel system assembled by PTX-loaded copolymer nanoparticles for sustained intraperitoneal chemotherapy of peritoneal carcinomatosis.
abstract: Intraperitoneal (IP) chemotherapy is a preferable treatment option for peritoneal carcinomatosis of malignancies by delivering chemotherapeutic drugs into the abdominal cavity. A persistent major challenge in IP chemotherapy is the need to provide effective drug concentration in the peritoneal cavity for an extended period of time. In the present work, the thermosensitive hydrogel system (PTX/PECT(gel)) assembled by PTX (paclitaxel)-loaded amphiphilic copolymer (PECT, poly (ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly (ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)) nanoparticles was developed for sustained IP chemotherapy of peritoneal carcinomatosis model. Cytotoxicity assay indicated that PECT hydrogel was biocompatible with very low cytotoxicity and PTX/PECT(gel) had enhanced cytotoxicity than free PTX. In vivo toxicity study demonstrated the biocompatibility and biosafety of PECT hydrogel as an IP chemotherapy carrier. The fluorescence imaging method was employed to monitor the intraperitoneal degradation of PECT hydrogel by labeling PECT with rhodamine B. PECT hydrogel with the dose of 200μL showed about 8days' retention time and most of the injected hydrogel was located in the intestine. The anti-tumor efficacy study was carried out in mice bearing CT26 intraperitoneal ascites fluid as colorectal peritoneal carcinomatosis model. The result showed that intraperitoneal administration of PTX/PECT(gel) could effectively suppress growth and metastasis of CT26 peritoneal carcinomatosis in vivo, compared with Taxol® group. The pharmacokinetic studies demonstrated that PTX/PECT(gel) could improve the bioavailability of PTX by being formulated in PECT hydrogel. Overall, sustained drug concentration at peritoneal levels in combination with drug in the form of nanoparticle contributes to the enhanced anti-tumor efficacy. Thus, our results suggested that PTX/PECT(gel) may have great potential applications in IP chemotherapy.
authors.affiliation: Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Xu
authors.affiliation: Tianjin Life Science Research Center and School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
authors.affiliation: Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China. Electronic address: liandongdeng@tju.edu.cn.
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
authors.affiliation: Tianjin Life Science Research Center and School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Electronic address: htang2002@yahoo.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000627:therapeutic use; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020100:Hydrogels; D011108:Polymers; D017239:Paclitaxel
keywords: Intraperitoneal chemotherapy; Nanoparticle; Paclitaxel; Thermosensitive hydrogel