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Drug Deliv Transl Res. 2014 Apr 1;4(2):203-9. doi: 10.1007/s13346-013-0190-7.

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

Author information

  • 1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 (USA) ; Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA).
  • 2Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 (USA).
  • 3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA) ; Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA).
  • 4Department of Pathology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287 (USA).
  • 5Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21231 (USA).
  • 6Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA) ; Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA).
  • 7Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA).
  • 8Department of Pathology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287 (USA) ; Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287 (USA) ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287 (USA).
  • 9Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 (USA) ; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA) ; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA) ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287 (USA) ; Center for Cancer Nanotechnology Excellence, Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA) ; Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA).

Abstract

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 (~ 13% w/w) and prolonged release (~ 13 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.

KEYWORDS:

biodegradable polymers; chemotherapy; controlled release; drug delivery

PMID:
24816829
PMCID:
PMC3956079
DOI:
10.1007/s13346-013-0190-7
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