title: Release of biologically functional interferon-alpha from a nanochannel delivery system.
abstract: Metastatic melanoma lesions often are unresectable due to their size and/or location near critical structures. These lesions represent a significant challenge for the oncologist, because radiation therapy and chemotherapy are infrequently successful in halting tumor growth. Of primary concern is the fact that these lesions are usually painful and present a cosmetic dilemma. We hypothesized that the development of a silicon-based nano-device capable of delivering antitumor compounds (e.g. immune modulators), locally, at a constant rate, to the tumor microenvironment could avoid the toxicity of systemic administration and the inconvenience of frequent clinic visits for local injections. Because of its diminutive size, such a device could be implanted using a minimally invasive procedure in close proximity to unresectable melanoma lesions. The current report uses interferon alpha-2b (IFN-alpha) as a model antitumor agent, since it is commonly used in the treatment of malignant melanoma and metastatic renal cell carcinoma. In this system, IFN-alpha is delivered directly to the tumor microenvironment by a novel nanochannel delivery system (nDS) that is capable of zero order release of small molecules. We have demonstrated that the IFN-alpha released from the nDS is functionally active on both host immune cells and a human melanoma cell line in vitro. This drug delivery platform could be used to develop alternative strategies for the treatment of unresectable tumors.
authors.affiliation: Department of Human Cancer Genetics, Division of Hematology and Oncology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Lesinski
authors.forename: Sadhana
authors.initials: S
authors.lastname: Sharma
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Varker
authors.forename: Piyush
authors.initials: P
authors.lastname: Sinha
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008545:Melanoma / Q000188:drug therapy* / Q000503:physiopathology; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D036103:Nanotechnology / Q000295:instrumentation* / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D016898:Interferon-alpha