title: Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model.
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.
authors.affiliation: Department 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).
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department 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).
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 (USA).
authors.forename: Joseph
authors.initials: J
authors.lastname: Wood
authors.affiliation: Department 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).
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department 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).
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Tang
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287 (USA).
authors.forename: Qi
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21231 (USA).
authors.forename: Brian W
authors.initials: BW
authors.lastname: Simons
authors.affiliation: Department 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).
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287 (USA).
authors.forename: Chi-Mu
authors.initials: CM
authors.lastname: Chuang
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA).
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Lai
authors.affiliation: Department 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).
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department 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).
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.affiliation: Department 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).
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
keywords: biodegradable polymers; chemotherapy; controlled release; drug delivery