Thermosensitive hydrogel system assembled by PTX-loaded copolymer nanoparticles for sustained intraperitoneal chemotherapy of peritoneal carcinomatosis

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• 作者：Shuxin Xu^a ; ^b ; ¹ ; Hongxia Fan^c ; ¹ ; Li Yin^a ; ^b ; Jianhua Zhang^a ; ^b ; Anjie Dong^a ; ^b ; Liandong Deng^a ; ^b ; ^{liandongdeng@tju.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Hua Tang^c ; ^{htang2002@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Intraperitoneal chemotherapy ; Thermosensitive hydrogel ; Nanoparticle ; Paclitaxel
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：104
• 期：Complete
• 页码：251-259
• 全文大小：2901 K

文摘

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 200 μL showed about 8 days’ 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.