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Improving intraperitoneal chemotherapeutic effect and preventing postsurgical adhesions simultaneously with biodegradable micelles

  • ChangYang Gong, PhD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
    • ,
  • Bing Yang, MD

      Affiliations

    • Department of Gynecology and Obstetrics, Second West China Hospital, Sichuan University, Chengdu, China
    • ,
  • ZhiYong Qian, PhD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
    • Corresponding Author InformationCorresponding author: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.
    • ,
  • Xia Zhao, MD

      Affiliations

    • Department of Gynecology and Obstetrics, Second West China Hospital, Sichuan University, Chengdu, China
    • ,
  • QinJie Wu, PhD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
    • ,
  • XiaoRong Qi, MD

      Affiliations

    • Department of Gynecology and Obstetrics, Second West China Hospital, Sichuan University, Chengdu, China
    • ,
  • YuJun Wang, PhD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
    • ,
  • Gang Guo, PhD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
    • ,
  • Bing Kan, PhD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
    • ,
  • Feng Luo, MD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
    • ,
  • YuQuan Wei, MD

      Affiliations

    • State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China

Received 6 December 2010; accepted 25 October 2011. published online 07 December 2011.
Corrected Proof

Abstract 

The two major concerns after cytoreductive surgery of abdominal and pelvic malignancies are residual tumors and peritoneal adhesions, which are inevitable and have great impact on prognosis. Therefore, to improve the intraperitoneal chemotherapeutic effect and prevent postsurgical adhesions simultaneously after surgery, we developed a novel strategy that combines the controlled drug delivery system (CDDS) with an antiadhesion barrier. Biodegradable poly(ethylene glycol)–poly(ɛ-caprolactone)–poly(ethylene glycol) (PECE) copolymer formed micelles in water, which turned instantly into a nonflowing gel at body temperature as a result of micellar aggregation. Effectiveness of doxorubicin-loaded PECE micelles (Dox-M) in improving intraperitoneal chemotherapeutic effect and preventing adhesions was investigated. Subsequently, we established a novel mouse model for postsurgical residual tumors and peritoneal adhesions, in which Dox-M could improve intraperitoneal chemotherapeutic effect and prevent postsurgical peritoneal adhesions simultaneously. Thus, it is a promising strategy to combine the CDDS and barrier method to improve the intraperitoneal chemotherapeutic effect and prevent peritoneal adhesions simultaneously after surgery.

Graphical Abstract 

A novel strategy to improve the effect of postsurgical intraperitoneal chemotherapy and prevent peritoneal adhesions simultaneously after cytoreductive surgery is proposed in this work, which combines a controlled drug delivery system with a barrier method. Our results indicated that the drug-loaded micelles showed an impressive antitumor and adhesion prevention effect in a novel mouse model of postsurgical residual tumors and peritoneal adhesion.

Key words: Micelles, Postsurgical adhesion, Intraperitoneal chemotherapy, Antiadhesion barrier, Drug delivery system

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 This work was financially supported by National 863 project (2007AA021902), Specialized Research Fund for the Doctoral Program of Higher Education (200806100065), New Century Excellent Talents in University (NCET-08-0371), Sichuan Key Technology R&D Program (2011SZ0219), and Chinese Key Basic Research Program (2010CB529906).

 Z-Y. Qian, Y-Q. Wei, X. Zhao, and C-Y. Gong designed the experiments. C-Y. Gong and B. Yang carried out experiments, analyzed the data, and wrote the manuscript. Z-Y. Qian corrected the manuscript. Q-J. Wu, X-R. Qi, and Y-J. Wang participated in the animal experiments. G. Guo participated in synthesizing the hydrogel. B. Kan and F. Luo participated in analyzing the data. All authors approved and read the final manuscript.

PII: S1549-9634(11)00516-8

doi:10.1016/j.nano.2011.10.010

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