Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model

JOURNAL OF CONTROLLED RELEASE

卷:123

Article

Kim, Grace Y. ; Tyler, Betty M. ; Tupper, Malinda M. ; Karp, Jeffrey M. ; Langer, Robert S. ; Brem, Henry ; Cima, Michael J.

关键词: drug delivery;    biodegradable polymer;    microchip;    tumor;    1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU);   

DOI  :  10.1016/j.jconrel.2007.08.003

来源: Elsevier

【 摘 要 】

Sustained local delivery of single agents and controlled delivery of multiple chemotherapeutic agents are sought for the treatment of brain cancer. A resorbable, multi-reservoir polymer microchip drug delivery system has been tested against a tumor model. The microchip reservoirs were loaded with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU was more stable at 37 degrees C within the microchip compared to a uniformly impregnated polymeric wafer (70% intact drug vs. 3 8%, at 48 h). The half-life of the intact free drug in the microchip was I I days, which is a marked enhancement compared to its half-life in normal saline and 10% ethanol (7 and 10 min, respectively) [P. Tepe, S.J. Hassenbusch, R. Benoit, J.H. Anderson, BCNU stability as a function of ethanol concentration and temperature, J. Neurooncol. 10 (1991) 121-127; P. Kari, W.R. McConnell, J.M. Finkel, D.L. Hill, Distribution of Bratton-Marshall-positive material in rnice following intravenous injections of nitrosoureas, Cancer Chemother. Pharmacol. 4 (1980) 243-248]. A syngeneic Fischer 344 9L gliosarcoma, rat model was used to study the tumoricidal efficacy of BCNU delivery from the microchip or homogeneous polymer wafer. A dose-dependent decrease in tumor size was found for 0. 17, 0.67, and 1.24 mg BCNU-microchips. Tumors treated with 1.24 mg BCNU-microchips showed significant tumor reduction (p = 0.001) compared to empty control microchips at two weeks. The treatment showed similar efficacy to a polymer wafer with the same dosage. The microchip reservoir array may enable delivery of multiple drugs with independent release kinetics and formulations. (C) 2007 Elsevier B.V. All rights reserved.

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