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 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 approximately 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.
Li
Yawen
Y
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ho Duc
Hong Linh
HL
Tyler
Betty
B
Williams
Tiffany
T
Tupper
Malinda
M
Langer
Robert
R
Brem
Henry
H
Cima
Michael J
MJ
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002250:Carbon Radioisotopes; D002330:Carmustine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004349:Drug Packaging; D004563:Electrochemistry; D005260:Female; D005898:Glass; D018316:Gliosarcoma / Q000188:drug therapy / Q000473:pathology; D008904:Miniaturization; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D047368:Tumor Burden / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D002250:Carbon Radioisotopes; D011092:Polyethylene Glycols; D002330:Carmustine