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Background

Microresevoir Theory

Fabrication(1,2)

Microreservoir actuation

Integrated microchip device

Advantages

References

Implantable device using microreservoir technology [10]

            In 2006, Santini et al. were capable of using a 100 reservoir microchip surgically implanted in dogs over a 6 month period to release a therapeutic polypeptide called nonapeptide leuprolide acetate, an analog of leuteinizing hormone-releasing hormone for prostate cancer and endometriosis treatment. The microchips used were 15 x 15 x 1 mm3 , with 100 individually addressable and electrothermally activated reservoirs each with a 300 nl volume. Approximately 25µg of lyophilized leuprolide in a matrix of solid polyethylene glycol that totaled about 200 nl in individual volumes for each reservoir. Reservoirs were sealed with spheres of indium-tin eutectic solder by thermocompression bonding then electrically connected to wireless communication hardware, power supply, and circuit boards of the in vivo implant. All these components are then hermetically sealed within a 4.5 x 5.5 x 1 cm3  laser welded titanium case with a volume of approximately 30 ml.

Figures: A cross sectional view electrical components, and a frontal view of the assembled implantable device. (Rights to images belongs to [10])

            Six devices were produced, each implanted in the subcutaneous tissue of different male beagle dogs. The number of reservoirs opened per dose (between 4 to 10 per release event) and frequency (every 1-4 weeks) were varied after 1 week of implantation to demonstrate controllability of remotely programmed drug release. To verify drug delivery, blood samples were taken at 1 hour intervals for 24 hours after reservoir release and analyzed by liquid chromatography.
            Results showed that in one dog, the device was slightly unreliable since leakage occurred after 14 weeks and thus a more reliable hermetic sealing method is being developed. Fibrous collagenous tissue also formed around the implants.  However, there was no significant obstruction of drug delivery which retained approximately 60% of leuprolide bioavailability. The average maximum drug concentration was around 5 to 11 ng/ml and took an average time of 2.0 to 3.2 hours to reach. The results are thus supportive of the feasibility to apply microchip-base implant technology for the purposes of therapeutic peptide and protein delivery.