Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model

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• 作者：Ming Yang (1) (9)
  Tao Yu (1) (9)
  Joseph Wood (1)
  Ying-Ying Wang (1) (9)
  Benjamin C. Tang (10) (2) (9)
  Qi Zeng (4)
  Brian W. Simons (7)
  Jie Fu (3) (9)
  Chi-Mu Chuang (4)
  Samuel K. Lai (11) (2)
  T.-C. Wu (4) (5) (6)
  Chien-Fu Hung (4) (5) (6)
  Justin Hanes (6) (8) (9)
  
• 关键词：Drug delivery ; Controlled release ; Chemotherapy ; Biodegradable polymers
• 刊名：Drug Delivery and Translational Research
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：4
• 期：2
• 页码：203-209
• 全文大小：4,245 KB
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• 作者单位：Ming Yang (1) (9)
  Tao Yu (1) (9)
  Joseph Wood (1)
  Ying-Ying Wang (1) (9)
  Benjamin C. Tang (10) (2) (9)
  Qi Zeng (4)
  Brian W. Simons (7)
  Jie Fu (3) (9)
  Chi-Mu Chuang (4)
  Samuel K. Lai (11) (2)
  T.-C. Wu (4) (5) (6)
  Chien-Fu Hung (4) (5) (6)
  Justin Hanes (6) (8) (9)
  
  1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, 21205, USA
  9. The Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD, 21287, USA
  10. Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA
  2. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD, 21218, USA
  4. Department of Pathology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD, 21287, USA
  7. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21231, USA
  3. Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD, 21287, USA
  11. Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Campus Box 7362, Chapel Hill, NC, 27599, USA
  5. Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA
  6. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA
  8. Center for Cancer Nanotechnology Excellence, Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD, 21218, USA
  
• ISSN：2190-3948

文摘

Intraperitoneal (IP) chemotherapy is more effective than systemic chemotherapy for treating advanced ovarian cancer, but is typically associated with severe complications due to high dose, frequent administration schedule, and use of non-biocompatible excipients/delivery vehicles. Here, we developed paclitaxel (PTX)-loaded microspheres composed of di-block copolymers of poly(ethylene glycol) and poly(sebacic acid) (PEG-PSA) for safe and sustained IP chemotherapy. PEG-PSA microspheres provided efficient loading (?3?% w/w) and prolonged release (?3?days) of PTX. In a murine ovarian cancer model, a single dose of IP PTX/PEG-PSA particles effectively suppressed tumor growth for more than 40?days and extended the median survival time to 75?days compared to treatments with Taxol? (47?days) or IP placebo particles (34?days). IP PTX/PEG-PSA was well tolerated with only minimal to mild inflammation. Our findings support PTX/PEG-PSA microspheres as a promising drug delivery platform for IP therapy of ovarian cancer and potentially other metastatic peritoneal cancers.