4.8 Article

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

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 106, Issue 1-2, Pages 138-145

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2005.04.009

Keywords

microelectromechanical systems (MEMS); drug delivery; BCNU; tumor; release kinetics

Funding

  1. NCI NIH HHS [U19-CA52857] Funding Source: Medline
  2. NIAID NIH HHS [R24 AI47739-01] Funding Source: Medline

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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.

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