title: On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device.
abstract: We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (Ø6 mm ×∼550 μm), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (Ø6 mm × 40 μm) with a laser-drilled aperture (∼100 × 100 μm(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations.
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Fatemeh Nazly
authors.initials: FN
authors.lastname: Pirmoradi
authors.forename: John K
authors.initials: JK
authors.lastname: Jackson
authors.forename: Helen M
authors.initials: HM
authors.lastname: Burt
authors.forename: Mu
authors.initials: M
authors.lastname: Chiao
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D007834:Lasers; D008280:Magnetics; D008567:Membranes, Artificial; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004129:Dimethylpolysiloxanes; D008567:Membranes, Artificial; D043823:Taxoids; D000077143:Docetaxel; C013830:baysilon