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.
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The authors declare no conflicts of interest.
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The experiments in this work comply with the current laws of the USA.
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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