An in-vivo evaluation of a MEMS drug delivery device using Kunming mice model

The use of MEMS implantable drug delivery pump device enables one to program the desired drug delivery profile in the device for individualized medicine treatment to patients. In this study, a MEMS drug delivery device is prepared and employed for in vivo applications. 12 devices are implanted subcutaneously into Kunming mice for evaluating their long term biocompatibility and drug-delivery efficiency in vivo. All the mice survived after device implantation surgery procedures. Histological analysis result reveals a normal wound healing progression within the tissues-to-device contact areas. Serum analysis shows that all measured factors are within normal ranges and do not indicate any adverse responses associated with the implanted device. Phenylephrine formulation is chosen and delivered to the abdominal cavity of the mice by using either the implanted MEMS device (experimental group) or the syringe injection method (control group). Both groups show that they are able to precisely control and manipulate the increment rate of blood pressure in the small animals. Our result strongly suggests that the developed refillable implantable MEMS devices will serve as a viable option for future individualized medicine applications such as glaucoma, HIV-dementia and diabetes therapy.

[1]  A. R. Kulkarni,et al.  Biodegradable polymeric nanoparticles as drug delivery devices. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[2]  Tao Wang,et al.  A Controlled-Release Drug Delivery System on a Chip Using Electrolysis , 2012, IEEE Transactions on Industrial Electronics.

[3]  Rui Hu,et al.  An Electrochemically Actuated MEMS Device for Individualized Drug Delivery: an In Vitro Study , 2013, Advanced healthcare materials.

[4]  E. Meng,et al.  A parylene bellows electrochemical actuator for intraocular drug delivery , 2009, TRANSDUCERS 2009 - 2009 International Solid-State Sensors, Actuators and Microsystems Conference.

[5]  Rui Hu,et al.  High reliability nanosandwiched Pt/Ti multilayer electrode actuators for on-chip biomedical applications. , 2014, The Analyst.

[6]  J. Kennedy,et al.  Synthesis, permeability and biocompatibility of tricomponent membranes containing polyethylene glycol, polydimethylsiloxane and polypentamethylcyclopentasiloxane domains. , 2003, Biomaterials.

[7]  Evangelia Bellas,et al.  Local Myotoxicity from Sustained Release of Bupivacaine from Microparticles , 2008, Anesthesiology.

[8]  Niveen M. Khashab,et al.  pH-triggered micellar membrane for controlled release microchips , 2011 .

[9]  Mark S Humayun,et al.  A refillable microfabricated drug delivery device for treatment of ocular diseases. , 2008, Lab on a chip.

[10]  E. Meng,et al.  High-Efficiency MEMS Electrochemical Actuators and Electrochemical Impedance Spectroscopy Characterization , 2012, Journal of Microelectromechanical Systems.

[11]  Po-Ying Li,et al.  An implantable MEMS micropump system for drug delivery in small animals , 2012, Biomedical microdevices.

[12]  M. Cima,et al.  A controlled-release microchip , 1999, Nature.

[13]  R Langer,et al.  Microchips as Controlled Drug-Delivery Devices. , 2000, Angewandte Chemie.

[14]  Po-Ying Li,et al.  A passive MEMS drug delivery pump for treatment of ocular diseases , 2009, Biomedical microdevices.

[15]  E. Meng,et al.  MEMS-enabled implantable drug infusion pumps for laboratory animal research, preclinical, and clinical applications. , 2012, Advanced drug delivery reviews.

[16]  John T Santini,et al.  Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device , 2006, Nature Biotechnology.

[17]  Robert Langer,et al.  Multi-pulse drug delivery from a resorbable polymeric microchip device , 2003, Nature materials.

[18]  K Miyamoto,et al.  Transscleral delivery of bioactive protein to the choroid and retina. , 2000, Investigative ophthalmology & visual science.

[19]  Peiyi Song,et al.  Preparation of biofunctionalized quantum dots using microfluidic chips for bioimaging. , 2014, The Analyst.

[20]  M. Staples.  Microchips and controlled-release drug reservoirs. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[21]  Tejal A Desai,et al.  Multi-reservoir bioadhesive microdevices for independent rate-controlled delivery of multiple drugs. , 2012, Small.

[22]  A. Giacca,et al.  A monolithic polymeric microdevice for pH-responsive drug delivery , 2009, Biomedical microdevices.

[23]  Rui Hu,et al.  A sustainable approach to individualized disease treatment: The Engineering of a multiple use MEMS drug delivery device , 2013, 2013 IEEE 5th International Nanoelectronics Conference (INEC).

[24]  Robert Langer,et al.  Small-scale systems for in vivo drug delivery , 2003, Nature Biotechnology.

[25]  Rui Hu,et al.  Moving towards individualized medicine with microfluidics technology , 2014 .

[26]  M. Gottesman.  Mechanisms of cancer drug resistance. , 2002, Annual review of medicine.

[27]  E. Meng,et al.  A Parylene Bellows Electrochemical Actuator , 2010, Journal of Microelectromechanical Systems.

[28]  Mark S Humayun,et al.  Mini Drug Pump for Ophthalmic Use , 2009, Current eye research.

[29]  Robert Langer,et al.  First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip , 2012, Science Translational Medicine.

[30]  Mark A. Burns,et al.  Surface-modified polyolefin microfluidic devices for liquid handling , 2005 .

[31]  Po-Ying Li,et al.  Implantable MEMS drug delivery device for cancer radiation reduction , 2010, 2010 IEEE 23rd International Conference on Micro Electro Mechanical Systems (MEMS).

[32]  Katsuya Harada,et al.  Chronic treatment with olanzapine via a novel infusion pump induces adiposity in male rats. , 2011, Life sciences.

[33]  N M Elman,et al.  An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care , 2009, Biomedical microdevices.

[34]  Sujeet K. Sinha,et al.  Bio-inspired polymeric patterns with enhanced wear durability for microsystem applications , 2011 .

[35]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[36]  Robert Langer,et al.  Biocompatibility and drug delivery systems , 2010 .

[37]  Y Zhang,et al.  The Gut as a Barrier to Drug Absorption , 2001, Clinical pharmacokinetics.

[38]  David Erickson,et al.  A robust, electrochemically driven microwell drug delivery system for controlled vasopressin release , 2009, Biomedical microdevices.

[39]  Po-Ying Li,et al.  An electrochemical intraocular drug delivery device , 2008, 2007 IEEE 20th International Conference on Micro Electro Mechanical Systems (MEMS).

[40]  Robert Langer,et al.  Application of Micro- and Nano-Electromechanical Devices to Drug Delivery , 2006, Pharmaceutical Research.

[41]  Nan-Chyuan Tsai,et al.  Review of MEMS-based drug delivery and dosing systems , 2007 .

[42]  Rui Hu,et al.  Approaches and Challenges of Engineering Implantable Microelectromechanical Systems (MEMS) Drug Delivery Systems for in Vitro and in Vivo Applications , 2012, Micromachines.

[43]  P. Renaud,et al.  Demonstration of cortical recording using novel flexible polymer neural probes , 2008 .