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

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 disso...

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Bibliographic Details
Published in:Journal of controlled release 2005-08, Vol.106 (1), p.138-145
Main Authors: Li, Yawen, Hong Linh Ho Duc, Tyler, Betty, Williams, Tiffany, Tupper, Malinda, Langer, Robert, Brem, Henry, Cima, Michael J.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Alkylating - pharmacokinetics
Antineoplastic Agents, Alkylating - therapeutic use
BCNU
Biological and medical sciences
Carbon Radioisotopes
Carmustine - pharmacokinetics
Carmustine - therapeutic use
Chemistry, Pharmaceutical
Drug delivery
Drug Delivery Systems - instrumentation
Drug Packaging
Electrochemistry
Female
General pharmacology
Glass
Gliosarcoma - drug therapy
Gliosarcoma - pathology
Medical sciences
Microelectromechanical systems (MEMS)
Miniaturization
Neoplasm Transplantation
Neoplasms, Experimental - drug therapy
Neoplasms, Experimental - pathology
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polyethylene Glycols - chemistry
Rats
Rats, Inbred F344
Release kinetics
Tumor
Tumor Burden - drug effects
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Summary: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∼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.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2005.04.009