In vivo delivery of BCNU from a MEMS device to a tumor model

被引:76
作者
Li, YW
Duc, HLH
Tyler, B
Williams, T
Tupper, M
Langer, R
Brem, H
Cima, MJ
机构
[1] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA
[2] Johns Hopkins Univ, Sch Med, Dept Neurol Surg, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[4] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
关键词
microelectromechanical systems (MEMS); drug delivery; BCNU; tumor; release kinetics;
D O I
10.1016/j.jconrel.2005.04.009
中图分类号
O6 [化学];
学科分类号
0703 [化学];
摘要
A drug delivery micrcoelectromechanical systems (MEMS) device was used to locally deliver a chemotherapeutic agent (BCNU) to an experimental tumor in rats. This MEMS device consists of an array of reservoirs etched into the silicon substrate. The drug release is achieved by the electrochemical dissolution of the gold membranes covering the reservoirs. A new Pyrex package was developed to improve the BCNU release kinetics and enhance device capacity. Co-formulation of BCNU with polyethylene glycol (PEG) led to complete and rapid release of drug in vivo. BCNU delivered from the MEMS device showed dose-dependent inhibiting effect on the tumor growth in the BCNU dosage range of 0.67 similar to 2 mg. BCNU delivered from the activated devices was as effective as equipotent subcutaneous injections of BCNU in inhibiting tumor growth. Further optimization using this MEMS device to deliver BCNU in combination with other therapeutic agents against the tumor challenge is possible because of the unique capability of the device to precisely control the temporal release profiles of multiple substances. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:138 / 145
页数:8
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