1. Iran University of Science and Technology 2. Iran University of Science and Technology 3. Tehran University 4. Iran University of Medical Science
Abstract
Introduction
Since the local, on demand, cancer therapy is a challenging clinical issue today, this paper presents the design, fabrication and characterization of a remotely controlled single reservoir drug delivery chip based on ionic polymer metal composite (ipmc) as an actuator. here, drug release was externally programmed and controlled wirelessly on demand by a communication circuit. the transmitter and receiver circuits were designed to control the release/sealed status remotely from even 7 cm distance while the transmitter and receiver were coupled magnetically. ipmc here was used as the moving cap of the reservoir, that when opens, lets the drug out on demand with a low received power of 20 mw. the novel simple design could release 100% content of the drug which is remarkable in comparison with the designs which need complicated optimizations of diffuser, nuzzle and ipmc diaphragm pump leading to an incomplete release. to make sure that we have no leakage in the sealed mode, ipmc was attached to a polydimethylsiloxane (pdms) support film. biocompatibility of all the components of the chip were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (mtt) assay. (180 words)
Methods
In the present study, a single reservoir drug delivery chip was fabricated by using ipmc actuator as the cap of the reservoir. the whole process contained four steps: a) fabrication of the ipmc actuator by chemical electroless plating; b) fabrication of the single reservoir chip on a silicon wafer by high technique photolithography; c) bonding the ipmc as the cap to the reservoir and d) finally designing the transmitter and receiver circuits and coupling them by electromagnetic waves and linking the receiver to the single reservoir chip so that the drug release can be conducted on demand. the whole system was tested to be bio compatible by encapsulation it in pdms polymer. (112 words)
Results
The reservoir was smooth edged supported by sem images with depth of 200 micron. the ipmc actuator was well fabricated supported by sem (scanning electron microscopy) and afm (atomic force microscopy) images. actuation and subsequently the drug release was controlled by a manipulated communication system based on transmitter and receiver circuits. they were linked with each other by electromagnetic waves with 2 mhz frequency and from 5 cm distance. in vitro drug release was conducted by ph analysis of release of an acidic drug from the reservoir by applying voltage to ipmc actuator. in vitro biocompatibility of the chip was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (mtt) assay (sigma-aldrich, usa) using breast cancer mcf7 cell line (atcc, usa) as a standard breast cell in cytotoxicity assays. the mtt assay was performed based on standard protocols. the results of biocompatibility studies on breast cancer cell line through mtt assay reveals 97% and 94% cell viability for silicon chip substrate and pdms encapsulator respectively. (161 words)
Conclusion
The single reservoir, wirelessly controlled drug delivery chip was designed using ipmc actuator as the gate of the reservoir. the drug was released on demand by generating electromagnetic waves that were converted to electrical voltage and transferred to ipmc actuator in receiver section on the chip. the system was tested to be bio compatible to get implanted in the body. (60 words)
Keywords
Drug delivery; ionic polymer metal composite; actuator; drug reservoir; remote control (11 words)
