Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo.
Drug carrier particles composed of poly(ethylene glycol)-co-poly(sebacic acid) (PEG-PSA) have been shown capable of efficient aerosolization into model lungs and the ability to rapidly penetrate human mucus. Here, we develop PEG-PSA particles (Etop/PEG-PSA) that encapsulate up to 40% etoposide by weight in a one step process, release it continuously for 6 days in vitro, and maintain its cytotoxic activity against a human lung tumor cell line in vitro. We further show that Etop/PEG-PSA injected intratumorally effectively suppress human lung tumor growth in a xenograft mouse model, with 100% survival after 31 days. In contrast, 0% survival was observed by day 24 in animals that received free etoposide (either intratumoral or intraperitoneal administration) or placebo particles intratumorally. These findings support PEG-PSA as a drug delivery platform for improved local therapy of cancer.
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Benjamin C
BC
Tang
Jie
J
Fu
D Neil
DN
Watkins
Justin
J
Hanes
D000818:Animals; D045744:Cell Line, Tumor; D003652:Decanoic Acids / Q000737:chemistry*; D003998:Dicarboxylic Acids / Q000737:chemistry*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005047:Etoposide / Q000008:administration & dosage* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000737:chemistry*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D011092:Polyethylene Glycols; D005047:Etoposide; C011107:sebacic acid