How to cite this WIREs title:
WIREs Nanomed Nanobiotechnol

Impact Factor: 7.689

Microchips and controlled‐release drug reservoirs

Advanced Review

Mark Staples

Published Online: Jun 17 2010

DOI: 10.1002/wnan.93

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Abstract This review summarizes and updates the development of implantable microchip‐containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro‐ and nanoelectromechanical systems (MEMS or NEMS)‐based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip‐based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug‐medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. WIREs Nanomed Nanobiotechnol 2010 2 400–417 This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants

Final packaged implantable rapid drug delivery device. With kind permission from Springer Science + Business Media: Elman NM, Ho Duc HL, Cima MJ. An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care. (Reprinted with permission from Ref 21. Copyright 2009 Springer Science + Business Media).

[ Normal View | Magnified View ]

HPLC analysis of released vasopressin from the implantable rapid drug delivery device. With kind permission from Springer Science + Business Media: Elman NM, Ho Duc HL, Cima MJ. An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care. (Reprinted with permission from Ref 21. Copyright 2009 Springer Science + Business Media).

[ Normal View | Magnified View ]

Metallurgical microscope image of the part of a microchip exhibiting four polypyrrole (PPy) microelectrodes doped by sulfosalicylic acid (SSA) and one doped by adenosine triphosphate (ATP). Reprinted from Ge D, Tian X, Qi R, Huang S, Mu J, et al. A polypyrrole‐based microchip for controlled drug release. (Reprinted with permission from Ref 51. Copyright 2009 Elsevier).

[ Normal View | Magnified View ]

Pulsatile release of sulfosalicylic acid (SSA; open triangles) and adenosine triphosphate (ATP; filled circles) from each of the four drug‐containing microelectrodes on a single microchip over a period of several days. SSA was released at − 1.0 V; ATP was released at − 0.8 V. (Reprinted with permission from Ref 51. Copyright 2009 Elsevier).

[ Normal View | Magnified View ]

Debiotech miniature infusion pump (MIP) micropump: an implantable drug delivery system (IDDS). Debiotech products page. Available at: http://www.debiotech.com/products/msys/mip.html. (Accessed February 1, 2010. ©Copyright 1995–2002 Debiotech S.A. All rights reserved).

[ Normal View | Magnified View ]

Schematic of shape memory (SMA) alloy actuation micropump. With kind permission from Springer Science + Business Media: Amirouche F, Zhou Y, Johnson T. Current micropump technologies and their biomedical applications. (Reprinted with permission from Ref 58. Copyright 2009 Springer Science + Business Media).

[ Normal View | Magnified View ]

A representative section of a reservoir‐based microchip. Reprinted from Maloney JM, Uhland SA, Polito BF, Sheppard NF Jr, Pelta CM, et al. Electrothermally activated microchips for implantable drug delivery and biosensing. (Reprinted with permission from Ref 98. Copyright 2005 Elsevier).

[ Normal View | Magnified View ]

Exterior (left) and interior (right) views of assembled system: implantable multireservoir microchip drug delivery device. (Adapted with permission from Ref 68. Copyright 2006 Macmillan Publishers Ltd.).

[ Normal View | Magnified View ]

Three independent release events show the reproducible pulsatile release of hPTH 34‐amino acid N‐terminal fragment, hPTH(1–34) from a single multireservoir array. (Reprinted with permission from Ref 102. Copyright 2008 Springer).

[ Normal View | Magnified View ]

References

Jain, KK. Future of personalized medicine, Chapter 18. In: Textbook of Personalized Medicine. New York: Springer; 2009; 395–406.
Kim, K, Lee, J‐B. MEMS for drug delivery, Chapter 12. In: Wang, W, Soper, SA, eds. Bio‐MEMS: Technologies and Applications. Boca Raton, FL: CRC Press; 2006; 325–348.
Colombo, P, Sonvico, F, Colombo, G, Bettini, R. Novel platforms for oral drug delivery. Pharm Res 2009; 26: 601–611.
Santini, JT Jr, Richards, AC, Scheidt, RA, Cima, MJ, Langer, RS. Microchip technology in drug delivery. Ann Med 2000; 32: 377–379.
Santini, JT Jr, Cima, MJ, Langer, R. A controlled‐release microchip. Nature 1999; 397: 335–338.
Tao, SL, Desai, TA. Microfabricated drug delivery systems: from particles to pores. Adv Drug Deliv Rev 2003; 55: 315–328.
Gardner, DP. Microfabricated nanochannel implantable drug delivery devices: trends, limitations and possibilities. Exp Opin Drug Deliv 2006; 3: 479–487.
Shrivistava, S, Dash, D. Applying nanotechnology to human health. J Nanotech 2009; 2009: 1–14.
Shrivastava, S. Nanofabrication for drug delivery and tissue engineering. Digest J Nanomat 2008; 3: 257–263.
Tao, SL, Lubeleya, MW, Desai, TA. Bioadhesive poly(methyl methacrylate) microdevices for controlled drug delivery. J Con Rel 2003; 88: 215–228.
US Food and Drug Administration. Nanotechnology page. Available at: http://www.fda.gov/nanotechnology/. (Accessed February 1, 2010).
Sade, RM, American Medical Association. Radio Frequency ID Devices in Humans, CEJA Report 5‐A‐07, 2007.
Staples, M, Daniel, K, Cima, MJ, Langer, R. Application of micro‐ and nano‐electromechanical devices to drug delivery. Pharm Res 2006; 23: 847–863.
Okumu, FW, Cleland, JL. Implants and injectables. In: Rathbone, MJ, Hadgraft, J, Roberts, MS, eds. Modified Release Drug Delivery Technology. New York: Marcel Dekkar; 2003; 633–638.
US Food and Drug Administration. Office of Combination Products page. Available at: http://www.fda.gov/oc/combination/. (Accessed January 2, 2010).
Portnoy, S, Koepke, S. Obtaining FDA approval of drug/device combination products. Part I: regulatory strategy considerations for preclinical testing. PharmaNet Consulting. Available at: http://www.pharmanet‐cro.com/pdf/whitepapers/Combo_Products.pdf. (Accessed January 2, 2010).
The Personalized Medicine Coalition. Home page. Available at: http://www.personalizedmedicinecoalition.org/sciencepolicy/personalmed‐101_overview.php. (Accessed January 2, 2010).
Amgen. Future of biotechnology in healthcare, Chapter 9. In: An Introduction to Biotechnology. 2009; 31–35. Available at: http://www. amgenscholars.eu/web/guest/future‐of‐biotechnology‐in‐healthcare. (Accessed January 2, 2010).
Heller, A. Integrated medical feedback systems for drug delivery. Am Inst Chem Eng J 2005; 51: 1054–1066.
Brunetti, P, Federici, MO, Benedetti, MM. The artificial pancreas. Artif Cells Blood Substit Immobil Biotechnol 2003; 31: 127–138.
Elman, NM, Ho Duc, HL, Cima, MJ. An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care. Biomed Microdevices 2009; 11: 625–631.
Robertson, TL, Hafezi, H. Personal paramedic, US20080058772A1.
Singer, I, Edmonds, HL. Head‐up tilt testing predicts syncope during ventricular tachycardia in implantable cardioverter defibrillator patients. J Interv Cardiol 1998; 11: 205–211.
Fonarow, GC, Feliciano, Z, Boyle, NG, Knight, L, Woo, MA, et al. Improved survival in patients with nonischemic advanced heart failure and syncope treated with implantable cardioverter–defibrillator. Am J Cardiol 2000; 85: 981–985.
Cavaco, D, Adragao, P, Aguiar, C, Neves, J, Abecasis, M, et al. Syncope in implantable cardioverter—defibrillator pacemaker dependent patients. Eur Heart J 2002; 23: 665–665.
Sanchez, JM, Katsiyiannis, WT, Gage, BF, Chen, J, Faddis, MN, et al. Implantable cardioverter–defibrillator therapy improves long‐term survival in patients with unexplained syncope, cardiomyopathy, and a negative electrophysiologic study. Heart Rhythm 2005; 2: 367–373.
Moran, EG, Mont, L. Incidence of syncope after ICD implantation: low or high? Eur Heart J 2006; 27: 2481–2482.
Hu, M, Lindemann, T, Göttsche, T, Kohnle, J, Zengerle, R, et al. Discrete chemical release from a microfluidic chip. J Microelectromech Syst 2007; 16: 786–794.
Genzyme Corporation. Form 10‐K. Annual Report for the fiscal year ended December 31, 2009. Available at: http://www.genzyme.com/corp/investors/XBRL/As‐Filed_2009_GENZ_Form_10‐K.pdf. (Accessed May 1, 2010).
Genzyme website. The cost of enzyme replacement therapy. Available at: http://www.genzyme.com/commitment/patients/costof_treatment.asp. (Accessed January 2, 2010).
IMS Health. Decline in Growth of Prescription Drug Revenue is Forecast, New York: The Associated Press; Aug 9 2009.
BCC Research. Advanced Drug Delivery Systems: New Developments, New Technologies. 2009.
Madou, MJ. Fundamentals of Microfabrication. 2nd ed. Boca Raton, FL: CRC Press; 2002.
Ainslie, KM, Desai, TA. Microfabricated implants for applications in therapeutic delivery, tissue engineering, and biosensing. Lab Chip 2008; 8: 1864–1878.
Betancourt, T, Brannon‐Peppas, L. Micro‐ and nanofabrication methods in nanotechnological medical and pharmaceutical devices. Int J Nanomed 2006; 1: 483–495.
Santini, JT Jr, Cima, MJ, Langer, RS. Method for making microchip reservoir device, US20070047926A1, 2008.
Santini, JT Jr, Cima, MJ, Langer, RS. Microchip drug delivery devices, US007070590B1, 2006.
Santini, JT Jr, Cima, MJ, Langer, RS. Medical device with array of electrode‐containing reservoirs, US007070592B2, 2006.
Santini, JT Jr, Hutchinson, CE, Uhland, SA, Cima, MJ, Langer, RS, et al. Microfabricated devices for the delivery of molecules into a carrier fluid, US006537256B2, 2003.
Grayson, AR, Johnson, A, Flynn, N, Li, Y, Cima, MJ, et al. A bioMEMS review: MEMS technology for physiologically integrated devices. Proc IEEE 2004; 92: 6–21.
LaVan, DA, McGuire, T, Langer, R. Small‐scale systems for in vivo drug delivery. Nat Biotechnol 2003; 21: 1184–1191.
Tsai, H‐KA, Ma, K‐S, Wang, C, Xu, H, Wang, C, et al. Development of integrated protection for a miniaturized drug delivery system. Smart Mater Struct 2007; 16: S295–S299.
Tsai, H‐KA, Madou, M. Microfabrication of bilayer polymer actuator valves for controlled drug delivery. JALA 2007; 12: 291–295.
Gilad, P. Electronically‐controlled device for release of drugs, proteins, and other organic or inorganic chemicals, US20090216176A1, 2009.
Langereis, G, Iordanov, VP, van Bruggen, MPB, Krijnsen, HC. Device for the controlled release of a substance and method of releasing substance, US20090099553A1, 2009.
Xu, H, Wang, C, Wang, C, Zoval, J, Madou, M. Polymer actuator valves toward controlled drug delivery application. Biosens Bioelectron 2006; 21: 2094–2099.
Wood, K, Zacharia, N, Cunningham, PH, Delongchamp, D. Electronically‐degradable layer‐by‐layer thin films, US20090088679A1, 2009.
Santini, JT Jr, Richards, AC, Scheidt, R, Cima, MJ, Langer, R. Microchips as implantable drug delivery devices. Angew Chem Int Ed Engl 2000; 39: 2396–2407.
Razzacki, SZ. Integrated microsystems for controlled drug delivery. Adv Drug Deliv Rev 2004; 56: 185–198.
Grayson, ACR, Shawgo, RS, Li, Y, Cima, MJ. Electronic MEMS for triggered delivery. Adv Drug Deliv Rev 2003; 56: 173–184.
Ge, D, Tian, X, Qi, R, Huang, S, Mu, J, et al. A polypyrrole‐based microchip for controlled drug release. Electrochim Acta 2009; 55: 271–275.
d`Alarcao, M, Calias, P. Electrochemically degradable polymers, US20090024074A1, 2009.
Gravesen, P, Branebjerg, J, Jensen, OS. Micro Fluidics—a review. J Micromech Microeng 1993; 3: 168–182.
Shoji, S, Esashi, M. Microflow devices and systems. J Micromech Microeng 1994; 4: 157–171.
Sato, S, Ebert, CD, Kim, SW. Prevention of insulin self‐association and surface adsorption. J Pharm Sci 1983; 72: 228–232.
Brennan, JR, Gebhart, SS, Blackard, WG. Pump‐induced insulin aggregation. A problem with the Biostator. Diabetes 1985; 34: 353–359.
der Veen, ME, van Iersel, DG, van der Goot, AJ, Boom, RM. Shear‐induced inactivation of alpha‐amylase in a plain shear field. Biotechnol Prog 2004; 20: 1140–1145.
Amirouche, F, Zhou, Y, Johnson, T. Current micropump technologies and their biomedical applications. Microsys Tech 2009; 15: 647–666.
White, NM. The origins and the future of microfluidics. Nature 2006; 442: 368–373.
Smits, JG. Piezoelectric micropump with three valves working peristaltically. Sens Actuators 1990; A21–A23: 203–206.
Reynaerts, D, Peirs, J, Brussel, HV. An implantable drug delivery system based on shape memory alloy micro‐actuation. Sens Actuators A Phys 1997; 61: 455–462.
Benard, WL, Kahn, HA, Heuer, H, Huff, MA. Thin film shape memory alloy actuated micropumps. J Microelectromech Syst 1998; 7: 245–251.
Chen, L, Choo, J, Yan, B. The microfabricated electrokinetic pump: a potential promising drug delivery technique. Exp Opin Drug Deliv 2007; 4: 119–129.
Debiotech products page. Available at: http://www. debiotech.com/products/msys/mip.html. (Accessed January 2, 2010).
Sangkwon, N, Ridgeway, S, Cao, L. Theoretical and experimental study of fluid behavior of a peristaltic micropump. Proceedings of 15th Biennial University/Government/Industry Microelectronics Symposium, Boise State University, Boise, Idaho, 2003; 312–316.
Cao, L, Mantell, LS, Polla, D. Design and simulation of an implantable medical drug delivery system using microelectromechanical systems technology. Sens Actuators A Phys 2001; 94: 117–125.
Fiering, J, Mescher, M. Drug delivery apparatus, US20080009836A1, 2008.
Prescott, JH, Lipka, S, Baldwin, S, Sheppard, NF Jr, Maloney, JM, et al. Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device. Nat Biotechnol 2006; 24: 437–438.
Prescott, JH, Krieger, TJ, Lipka, S, Staples, MA. Dosage form development, in vitro release kinetics, and in vitro–in vivo correlation for leuprolide released from an implantable multi‐reservoir array. Pharm Res 2007; 24: 1252–1261.
Petersen, KE. Silicon as a mechanical material. Proc IEEE 1982; 70: 420–457.
Bhushan, B, Burton, Z. Adhesion and friction properties of polymers in microfluidic devices. Nanotechnology 2005; 16: 467.478.
Guse, C, Koennings, S, Blunk, T, Siepmann, J, Goepferich, A. Programmable implants‐from pulsatile to controlled release. Int J Pharm 2006; 314: 161–169.
Haykin, S. Neural Networks: A Comprehensive Foundation. New York: Prentice Hall; 1998.
Ahmed, FE. Artificial neural networks for diagnosis and survival prediction in colon cancer. Mol Cancer 2005; 4: 29.
Achanta, AS, Kowalski, JG, Rhodes, CT. Artificial neural networks: implications for pharmaceutical sciences. Drug Dev Ind Pharm 1995; 21: 119–155.
Agatonovic‐Kustrin, S, Beresford, R. Basic concepts of artificial neural network (ANN) modeling and its application in pharmaceutical research. J Pharm Biomed 2000; 22: 717–727.
Zdeblick, MJ, Robertson, T. Medical diagnostic and treatment platform using near‐field wireless communication of information within a patient`s body, US20080306359A1, 2008.
Zdeblick, MJ, Thompson, A, Pikelny, A, Robertson, T. Pharma‐informatics system, US20080284599A1, 2008.
Smith, S, Tang, TB, Stevenson, JTM, Flynn, BW, Reekie, HM, et al. Miniaturized drug delivery system with wireless power transfer and communication. IET Nanobiotechnol 2007; 1: 80–86.
U.S. Food and Drug Administration. Draft Guidance for Industry and FDA Staff Radio‐Frequency Wireless Technology in Medical Devices. Draft released for comment on January 3, 2007. Available at: http://www.fda.gov/downloads/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/ ucm077272.pdf. (Accessed May 1, 2010).
Sheppard, N, Santini, JT Jr, Cima, MJ, Langer, RS, Ausiello, D. Method for wirelessly monitoring implanted medical device, US20080221555A1, 2008.
de Avila, J. Your iPhone just called: your blood‐sugar is high. Wall St J (East Ed) December 21, 2009; D1–D2.
Bequette, BW. A critical assessment of algorithms and challenges in the development of a closed‐loop artificial pancreas. Diabetes Technol Ther 2005; 7: 28–47.
Tang, TB, Smith, S, Flynn, BW, Stevenson, JTM, Gundlach, AM, et al. Implementation of wireless power transfer and communications for an implantable ocular drug delivery system. IET Nanobiotechnol 2008; 2: 72–79.
Santini, JT Jr, Ausiello, D. Pre‐clinical animal testing method, US20080083041A1, 2008.
Smith, S, Tang, TB, Terry, JG, Stevenson, JTM, Flynn, BW, et al. Development of a miniaturised drug delivery system with wireless power transfer and communication. IET Nanobiotechnol 2007; 1: 80–86.
Coppeta, JR, Uhland, SA, Polito, BF, Sheppard, NF Jr, Feakes, CM, et al. Hermetically sealed devices for controlled release or exposure of reservoir contents, US20070036835A1, 2007.
Daniel, K, Duc, HLH, Cima, MJ, Langer, RS. Controlled release microchips, Chapter 9. In: Youan, B‐BC, ed. Chronopharmaceutics. New York: John Wiley %26 Sons; 2009; 187–215.
Sharma, S, Nijdam, AJ, Sinha, PM, Walczak, RJ, Liu, X, et al. Controlled‐release microchips. Exp Opin Drug Deliv 2006; 3: 379–394.
Huang, W‐C, Hu, S‐H, Liu, K‐H, Chen, S‐Y, Liu, D‐M. A flexible drug delivery chip for the magnetically‐controlled release of anti‐epileptic drugs. J Controlled Release 2009; 139: 221–228.
Intra, J, Glasgow, JM, Mai, HQ, Salem, AK. Pulsatile release of biomolecules from polydimethylsiloxane (PDMS) chips with hydrolytically degradable seals. J Controlled Release 2008; 127: 280–287.
Kim, GY, Tyler, BM, Tupper, MM, Karp, JM, Langer, RS, et al. Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model. J Controlled Release 2007; 123: 172–178.
Richards, AC, Santini, JT Jr, Cima, MJ, Langer, RS. Multi‐reservoir device for controlled drug delivery, US20060189963A1, 2006.
Shawgo, RS, Grayson, ACR, Li, Y, Cima, MJ. BioMEMS for drug delivery. Curr Opin Solid State 2002; 6: 329–334.
Li, Y, Shawgo, RS, Tyler, BM, Henderson, PT, Vogel, JS, et al. In vivo release from a drug delivery MEMS device. J Controlled Release 2004; 100: 211–219.
Li, Y, Duc, HLH, Tyler, BM, Williams, T, Tupper, M, et al. In vivo delivery of BCNU from a MEMS device to a tumor model. J Controlled Release 2005; 106: 138–145.
Chung, A, Kim, D, Erickson, D. Electrokinetic microfluidic devices for rapid, low power drug delivery in autonomous microsystems. Lab Chip 2008; 8: 330–338.
Maloney, JM, Uhland, SA, Polito, BF, Sheppard, NF Jr, Pelta, CM, et al. Electrothermally activated microchips for implantable drug delivery and biosensing. J Controlled Release 2005; 109: 244–255.
Uhland, SA, Polito, B, Maloney, JM, Sheppard, NF, Herman, SJ, et al. Method for making device for controlled reservoir opening by electrothermal ablation, US20080168921A1, 2008.
Santini, JT Jr, Cima, MJ, Langer, RS. Method for operating microchip reservoir device. US20080051766A1, 2008.
Johnson, AM, Cima, MJ, Langer, RS. Microscale lyophilization and drying methods for the stabilization of molecules, US007354597B2, 2008.
Proos, ER, Prescott, JH, Staples, MA. Long‐term stability and in vitro release of hPTH(1–34) from a multi‐reservoir array. Pharm Res 2008; 25: 1387–1395.
Prescott, JH, Krieger, T, Proos, ER. Control of drug release by transient modification of local microenvironments, US007488316B2, 2009.
Ausiello, D, Santini, JT Jr, Herman, SJ, Prescott, JH, Uhland, SA, et al. Implantable device for controlled, extended delivery of parathyroid hormone, US20090163895A1, 2009.
Ausiello, D, Santini, JT Jr, Herman, SJ, Prescott, JH. Method and device for the controlled delivery of parathyroid hormone, US20040082937A1, 2004.
Liu, X, Pettway, GJ, McCauley, LK, Ma, PX. Pulsatile release of parathyroid hormone from an implantable delivery system. Biomaterials 2007; 28: 4124–4131.
Santini, JT Jr, Hutchinson, CE, Proos, ER. Medical and dental implant devices for controlled drug delivery, US20070016163A1, 2007.
Martinson, JB, Stark, JG, Hanson, TJB, Backes, SJ. Instrumented orthopedic and other medical implants, US20060271112A1, 2006.
Santini, JT Jr, Cima, MJ, Langer, RS, Ausiello, D, Sheppard, NF. Method of opening reservoir of containment device, US20080221557A1, 2008.
Santini, JT Jr, Cima, MJ, Langer, RS, Ausiello, D, Sheppard, NF. Method of actuating implanted medical device. US20080071252A1, 2008.
Sugiura, S, Sumaru, K, Ohi, K, Hiroki, K, Takagi, T, et al. Photoresponsive polymer gel microvalves controlled by local light irradiation. Sens Actuators, A 2007; 140: 176–184.
Johnson, MT, Kurt, R. Device for the controlled release of a predefined quantity of a substance, US20080208174A1, 2008.
Langer, R. Drugs on target. Science 2001; 293: 58–59.
Traitel, T, Goldbart, R, Kost, J. Smart polymers for responsive drug‐delivery systems. J Biomater Sci Polym Ed 2008; 19: 755–767.
Satarkar, NS, Hilt, JZ. Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release. J Controlled Release 2008; 130: 246–251.
Yoshida, R, Sakai, T, Hara, Y, Maeda, S, Hashimoto, S, et al. Self oscillating gel as novel biomimetic materials. J Controlled Release 2009; 140: 186–193.
Yoshida, R. Design of functional polymer gels and their application to biomimetic materials. Curr Org Chem 2005; 9: 1617–1641.
Okano, T, ed. Biorelated Polymers and Gels: Controlled Release and Applications in Biomedical Engineering. London: Academic Press; 1998.
Peppas, NA, Hilt, JZ, Khademhosseini, A, Langer, R. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater (Weinheim, Ger) 2006; 18: 1345–1360.
Jun, SB, Hynd, MR, Dowell‐Mesfin, NM, Al‐Kofahi, Y, Roysam, B, et al. Modulation of cultured neural networks using neurotrophin release from hydrogel‐coated microelectrode arrays. J Neural Eng 2008; 5: 203–213.
Kikuchi, A, Okano, T. Pulsatile drug release control using hydrogels. Adv Drug Deliv Rev 2002; 54: 53–77.
Kataoka, K, Miyazaki, H, Bunya, M, Okano, T, Sakurai, Y. Totally synthetic polymer gels responding to external glucose concentration: their preparation and application to on‐off regulation of insulin release. J Am Chem Soc 1998; 120: 12694–12695.
Matsumoto, A, Yoshida, R, Kataoka, K. Glucose‐responsive polymer gel bearing phenylborate derivative as a glucose‐sensing moiety operating at the physiological pH. Biomacromolecules 2004; 5: 1038–1045.
Hoffman, AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev 2002; 43: 3–12.
Miyata, T, Uragami, T, Nakamae, K. Biomolecule‐sensitive hydrogels. Adv Drug Deliv Rev 2002; 54: 79–98.
Kiser, PF, Wilson, G, Needham, D. A synthetic mimic of the secretory granule for drug delivery. Nature 1998; 394: 459–462.
Yeghiazarian, LL, Wiesner, U, Montemagno, CD. Volume phase transition to induce gel movement, US007313917B2, 2008.
Phyllis Gardner, P. Microfabricated nanochannel implantable drug delivery devices: trends, limitations and possibilities. Adv Drug Deliv Rev 2006; 3: 479–487.
Randall, CL, Leong, TG, Bassik, N, Gracias, DH. 3D lithographically fabricated nanoliter containers for drug delivery. Adv Drug Deliv Rev 2007; 59: 1547–1561.
Boston Scientific Corporation. Form 10‐K. Annual Report for the fiscal year ended December 31, 2004. Available at: http://phx.corporate‐ir.net/phoenix.zhtml?c = 62272%26p = irol‐sec%26secCat01Enhanced.1_rs = 11%26secCat01Enhanced.1_rc = 10%26control_selectgroup = Annual%20Filings. (Accessed May 1, 2010).
Pfizer Inc. 2007 Financial Report. Available at: http://media.pfizer.com/files/annualreport/2007/financial/financial2007.pdf. (Accessed May 1, 2010).
Bayer, AG. Bayer Annual Report 2006. Available at: http://www.bayer.com/en/GB‐2006‐en.pdfx. (Accessed May 1, 2010).
Vyteris, Inc. Form 10‐Q Quarterly Report. Filed November 13, 2009. Available at: http://investor.vyteris.com/. (Accessed May 1, 2010).
Alaeea, M, Moghadama, SH, Sayyara, P, Atyabia, F, Dinarvanda, R. Preparation of a reservoir type levonorgestrel delivery system using high molecular weight poly L‐lactide. Iran J Pharm Res 2009; 8: 87–93.

Further Reading

Papazoglou, ES, Parthasarathy, A. BioNanotechnology. Synthesis Lectures on Biomedical Engineering 2007, 2:1–139. DOI: https://doi.org/10.2200/S00051ED1V01Y200610BME007.
Saliterman, SS. Fundamentals of BioMEMS and medical microdevices. Bellingham, WA: SPIE Press; 2006.
Selected Surveys and Introductions to Aspects of MEMS‐based Technology
Jain, KK. Chapter 1, Drug delivery systems overview. Pp 1‐50 in Jain, KK, ed., Methods in Molecular Biology, Vol. 437: Drug Delivery Systems. Totowa, NJ: Humana Press; 2008. DOI: https://doi.org/10.1007/978‐1‐59745‐210‐6_1.
James, T, Mannoor, MS, Ivanov, DV. Review: BioMEMS –advancing the frontiers of medicine. Sensors 2008, 8:6077–6107.
Kumar, R. The emerging therapy of tomorrow with nanomedicine: present status. Internet J Neural 2008, 10(1).
Selected Overviews,, Specific Applications of MEMS‐based Therapies
Biondi, M, Ungaro, F, Quaglia, F, Netti, PA. Controlled drug delivery in tissue engineering. Adv Drug Deliv Rev 2008, 60:229–242. DOI: https://doi.org/10.1016/j.addr.2007.08.038.
Elder, JB, Hoh, DJ, Oh, BC, Heller, AC, Liu, CY, Apuzzo, ML. The future of cerebral surgery: a kaleidoscope of opportunities. Neurosurgery 2008, 62:1555‐79; discussion 1579‐82. https://doi.org/10.1227/01.NEU.0000316426.13241.A9
Farokhzad, OC, Dimitrakov, JD, Karp, JM, Khademhosseini, A, Freeman, MR, Langer, R. Drug delivery systems in urology‐getting ‘smarter’. Urology 2006, 68:463–9. DOI: https://doi.org/10.1016/j.urology.2006.03.069.
Moldovan, NI, Ferrari, M. Prospects for microtechnology and nanotechnology in bioengineering of replacement microvessels. Arch Pathol Lab Med 2002, 126:320–4.
Raghava, S, Goel, G, Kompella, UB. Chapter 22, Ophthalmic applications of nanotechnology. Pp 413‐435 in Tombran‐Tink, J, Barnstable, CJ, eds., Ocular transporters in ophthalmic diseases and drug delivery. Totowa, NJ: Humana Press; 2008.
Wang, PP, Frazier, J, Brem, H. Local drug delivery to the brain. Adv Drug Deliv Rev 2002, 16:987–1013.
FDA (Home, Office of Combination Products): http://www.fda.gov/oc/combination/
MicroCHIPS (Home): http://www.mchips.com/
Debiotech, SA: http://www.debiotech.com/home/index.html (Home) http://www.debiotech.com/products/msys/insulinpump.html (Insulin Nanopump^TM)

Resources

Further Reading

Books

Papazoglou, ES, Parthasarathy, A. BioNanotechnology. Synthesis Lectures on Biomedical Engineering 2007, 2:1-139. doi: 10.2200/S00051ED1V01Y200610BME007.
Saliterman SS. Fundamentals of BioMEMS and medical microdevices. Bellingham, WA: SPIE Press; 2006.

Articles

Selected Surveys and Introductions to Aspects of MEMS-based Technology

Jain, KK. Chapter 1, Drug delivery systems overview. Pp 1-50 in Jain, KK, ed., Methods in Molecular Biology, Vol. 437: Drug Delivery Systems. Totowa, NJ: Humana Press; 2008. doi:10.1007/978-1-59745-210-6_1.
James, T, Mannoor, MS, Ivanov, DV. Review: BioMEMS –advancing the frontiers of medicine. Sensors 2008, 8:6077-6107.
Kumar, R. The emerging therapy of tomorrow with nanomedicine: present status. Internet J Neural 2008, 10(1)[no page numbers].

Selected Overviews, Specific Applications of MEMS-based Therapies

Biondi, M, Ungaro, F, Quaglia, F, Netti, PA. Controlled drug delivery in tissue engineering. Adv Drug Deliv Rev 2008, 60:229-242. doi:10.1016/j.addr.2007.08.038.
Elder JB, Hoh DJ, Oh BC, Heller AC, Liu CY, Apuzzo ML. The future of cerebral surgery: a kaleidoscope of opportunities. Neurosurgery 2008, 62:1555-79; discussion 1579-82. doi: 10.1227/01.NEU.0000316426.13241.A9
Farokhzad OC, Dimitrakov JD, Karp JM, Khademhosseini A, Freeman MR, Langer R. Drug delivery systems in urology-getting “smarter”. Urology 2006, 68:463-9. doi:10.1016/j.urology.2006.03.069.
Moldovan, NI, Ferrari, M. Prospects for microtechnology and nanotechnology in bioengineering of replacement microvessels. Arch Pathol Lab Med 2002, 126:320-4.
Raghava, S, Goel, G, and Kompella, UB. Chapter 22, Ophthalmic applications of nanotechnology. Pp 413-435 in Tombran-Tink, J, Barnstable, CJ, eds., Ocular transporters in ophthalmic diseases and drug delivery. Totowa, NJ: Humana Press; 2008.
Wang, PP, Frazier, J, Brem H. Local drug delivery to the brain. Adv Drug Deliv Rev 2002, 16:987-1013.

Websites

FDA (Home, Office of Combination Products): http://www.fda.gov/oc/combination/
MicroCHIPS (Home): http://www.mchips.com/
Debiotech S.A.:
http://www.debiotech.com/home/index.html (Home)
http://www.debiotech.com/products/msys/insulinpump.html (Insulin Nanopump^TM)

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts