In vivo release from a drug delivery MEMS device

Yawen Li, Rebecca S. Shawgo, Betty Tyler, Paul Henderson, John S. Vogel, Aron Rosenberg, Phillip B. Storm, Robert Langer, Henry Brem, Michael J. Cima

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

A drug delivery microelectromechanical systems (MEMS) device was designed to release complex profiles of multiple substances in order to maximize the effectiveness of drug therapies. The device is based on micro-reservoirs etched into a silicon substrate that contain individual doses of drug. Each dose is released by the electrochemical dissolution of the gold membrane that covers the reservoir. The first in vivo operation of this device was reported in this study. Subcutaneous release was demonstrated in rats using two tracer molecules, fluorescein dye and radiolabeled mannitol, and one radiolabeled chemotherapeutic agent, carmustine (BCNU). BCNU was chosen because of the need to improve the direct delivery of chemotherapy to malignant tumors. The spatial profile of fluorescein dye release from the drug delivery device was evaluated by fluorimetry, the temporal profile of 14C labeled mannitol release was evaluated by liquid scintillation counting, and the temporal profile of 14C labeled BCNU release was evaluated by accelerator mass spectrometry (AMS). Release profiles obtained from injected controls were compared with those from activated devices. The in vivo dye release results showed high concentration of fluorescein in the flank tissue surrounding the devices 1 h after activation. The 14C labeled mannitol released from the drug delivery devices was rapidly cleared (1 day) from the rat urine. In vivo release of 14C labeled BCNU from activated devices showed slightly slower kinetics than the injected and in vitro controls, and the time to reach the steady-state plasma 14C concentration was on the order of 1 h. All these results demonstrated the capability of this drug delivery device to achieve localized delivery of various compounds with well-defined temporal profiles.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalJournal of Controlled Release
Volume100
Issue number2
DOIs
StatePublished - Nov 24 2004
Externally publishedYes

    Fingerprint

Keywords

  • Accelerator mass spectrometry (AMS)
  • Carmustine (BCNU)
  • Drug delivery
  • In vivo release kinetics
  • Microelectromechanical systems (MEMS)

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Li, Y., Shawgo, R. S., Tyler, B., Henderson, P., Vogel, J. S., Rosenberg, A., Storm, P. B., Langer, R., Brem, H., & Cima, M. J. (2004). In vivo release from a drug delivery MEMS device. Journal of Controlled Release, 100(2), 211-219. https://doi.org/10.1016/j.jconrel.2004.08.018