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

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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.

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Acknowledgments

This work was supported in part by NIH grants U54CA151838 (J.H.), P50CA098252 (T.W.), R01CA114425 (T.W.) and a National Science Foundation Graduate Research Fellowship (Y.-Y. W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. We thank M. Koontz, N. Forbes-McBean, and M. Chen for the technical and experimental assistance.

Conflict of interest

The authors declare no conflicts of interest.

Declaration of ethical standards

The experiments in this work comply with the current laws of the USA.

Author information

Author notes

  1. Benjamin C. Tang

    Present address: Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA

  2. Samuel K. Lai

    Present address: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Campus Box 7362, Chapel Hill, NC, 27599, USA

Authors and Affiliations

  1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, 21205, USA

    Ming Yang, Tao Yu, Joseph Wood & Ying-Ying Wang

  2. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD, 21218, USA

    Benjamin C. Tang & Samuel K. Lai

  3. Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD, 21287, USA

    Jie Fu

  4. Department of Pathology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD, 21287, USA

    Qi Zeng, Chi-Mu Chuang, T.-C. Wu & Chien-Fu Hung

  5. Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA

    T.-C. Wu & Chien-Fu Hung

  6. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA

    T.-C. Wu, Chien-Fu Hung & Justin Hanes

  7. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21231, USA

    Brian W. Simons

  8. Center for Cancer Nanotechnology Excellence, Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD, 21218, USA

    Justin Hanes

  9. The Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD, 21287, USA

    Ming Yang, Tao Yu, Ying-Ying Wang, Benjamin C. Tang, Jie Fu & Justin Hanes

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  1. Ming Yang
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Corresponding author

Correspondence to Justin Hanes.

Additional information

Ming Yang and Tao Yu contributed equally.

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Yang, M., Yu, T., Wood, J. et al. Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model. Drug Deliv. and Transl. Res. 4, 203–209 (2014). https://doi.org/10.1007/s13346-013-0190-7

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  • DOI: https://doi.org/10.1007/s13346-013-0190-7

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