Skip to main content

Advertisement

SpringerLink
Log in

Application of Micro- and Nano-Electromechanical Devices to Drug Delivery

  • Expert Review
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Micro- and nano-electromechanical systems (MEMS and NEMS)-based drug delivery devices have become commercially-feasible due to converging technologies and regulatory accommodation. The FDA Office of Combination Products coordinates review of innovative medical therapies that join elements from multiple established categories: drugs, devices, and biologics. Combination products constructed using MEMS or NEMS technology offer revolutionary opportunities to address unmet medical needs related to dosing. These products have the potential to completely control drug release, meeting requirements for on-demand pulsatile or adjustable continuous administration for extended periods. MEMS or NEMS technologies, materials science, data management, and biological science have all significantly developed in recent years, providing a multidisciplinary foundation for developing integrated therapeutic systems. If small-scale biosensor and drug reservoir units are combined and implanted, a wireless integrated system can regulate drug release, receive sensor feedback, and transmit updates. For example, an “artificial pancreas” implementation of an integrated therapeutic system would improve diabetes management. The tools of microfabrication technology, information science, and systems biology are being combined to design increasingly sophisticated drug delivery systems that promise to significantly improve medical care.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Abbreviations

ANN:

artificial neural network

AUC:

area under the plasma drug concentration vs. time curve; a measure of drug exposure

BCNU:

carmustine, an antineoplastic agent

Bio-IT:

convergence of bioscience with information technology

BLA:

biologics license application

DNA:

deoxyribonucleic acid

DRIE:

deep-reactive ion etching

FDA:

Food and Drug Administration of the United States Dept. of Health and Human Services

HGH:

humangrowth hormone

NDA:

New Drug Application

MEMS:

micro‐electromechanical systems

NEMS:

nano‐electromechanical systems

OCP:

Office of Combination Products

PDMS:

polydimethylsiloxane

PLA:

poly(L-lactic acid)

PLGA:

poly(lactide-co-glycolide)

PMA:

Premarket Approval (Device Application)

PMMA:

polymethylmethacrylate

PZT:

piezoelectric transducer

SD:

standard deviation

References

  1. F. W. Okumu J. L. Cleland (2003) Implants and injectables M. J. Rathbone J. Hadgraft M. S. Roberts (Eds) Modified Release Drug Delivery Technology Marcel Dekker New York 633–638

    Google Scholar 

  2. Foresight Nanotech Institute home page. http://www.foresight. org/ (accessed 10/05/05).

  3. U.S. Food and Drug Administration, Nanotechnology page. http://www.fda.gov/nanotechnology/ (accessed 10/05/05).

  4. U.S. Food and Drug Administration, Office of Combination Products page. http://www.fda.gov/oc/combination/ (accessed 10/05/05).

  5. A. C. R. Grayson R. S. Shawgo A. M. Johnson N. T. Flynn Y. Li M. J. Cima R. Langer (2004) ArticleTitleA bioMEMS review: MEMS technology for physiologically integrated devices Proc. IEEE 92 6–21 Occurrence Handle1:CAS:528:DC%2BD2cXht1eks70%3D Occurrence Handle10.1109/JPROC.2003.820534

    Article  CAS  Google Scholar 

  6. D. A. LaVan T. McGuire R. Langer (2003) ArticleTitleSmall-scale systems for in vivo drug delivery Nat. Biotechnol. 21 1184–1191 Occurrence Handle14520404 Occurrence Handle1:CAS:528:DC%2BD3sXns1Cltrw%3D Occurrence Handle10.1038/nbt876

    Article  PubMed  CAS  Google Scholar 

  7. M. J. Madou (2002) Fundamentals of Microfabrication EditionNumber 2 CRC Press Boca Raton

    Google Scholar 

  8. K. L. Ekinci and M. L. Roukes. Nanoelectromechanical systems. Rev. Sci. Instrum. 76:061101–12.

  9. M. E. Åkerman W. C. W. Chan P. Laakkonen S. N. Bhatia E. Ruoslahti (2002) ArticleTitleNanocrystal targeting in vivo Proc. Natl. Acad. Sci. USA 99 12617–12621 Occurrence Handle12235356 Occurrence Handle10.1073/pnas.152463399 Occurrence Handle1:CAS:528:DC%2BD38XnvFGiu7c%3D

    Article  PubMed  CAS  Google Scholar 

  10. J.-L. Lin D. Y. Petrovykh A. Kirakosian H. Rauscher F. J. Himpsel P. A. Dowben (2001) ArticleTitleSelf-assembled Fe nanowires using organometallic chemical vapor deposition and CaF2 masks on stepped Si(111) Appl. Phys. Lett. 78 829–831 Occurrence Handle1:CAS:528:DC%2BD3MXotlOksQ%3D%3D Occurrence Handle10.1063/1.1345830

    Article  CAS  Google Scholar 

  11. S. Kan T. Mokari E. Rothenberg U. Banin (2003) ArticleTitleSynthesis and size-dependent properties of zinc-blende semiconductor quantum rods Nat. Mater. 2 155–158 Occurrence Handle12612671 Occurrence Handle1:CAS:528:DC%2BD3sXhsFGhtL0%3D Occurrence Handle10.1038/nmat830

    Article  PubMed  CAS  Google Scholar 

  12. L. M. Ericson H. Fan H. Peng V. A. Davis W. Zhou J. Sulpizio Y. H. Wang R. Booker J. Vavro C. Guthy A. N. G. Parra-Vasquez M. J. Kim S. Ramesh R. Saini C. Kittrell G. Lavin H. Schimdt W. W. Adams W. E. Billups M. Pasquali W.-F. Hwang R. H. Hauge J. E. Fischer R. E. Smalley (2004) ArticleTitleMacroscopic, neat, single-walled carbon nanotube fibers Science 305 1447–1450 Occurrence Handle15353797 Occurrence Handle1:CAS:528:DC%2BD2cXntFartr0%3D Occurrence Handle10.1126/science.1101398

    Article  PubMed  CAS  Google Scholar 

  13. K. E. Petersen (1982) ArticleTitleSilicon as a mechanical material Proc. IEEE 70 420–457 Occurrence Handle1:CAS:528:DyaL3sXptl2jsQ%3D%3D Occurrence Handle10.1109/PROC.1982.12331

    Article  CAS  Google Scholar 

  14. F. Martin R. Walczak A. Boiarski M. Cohen T. West C. Cosentino M. Ferrari (2005) ArticleTitleTailoring width of microfabricated nanochannels to solute size can be used to control diffusion kinetics J. Control. Release 102 123–133 Occurrence Handle15653139 Occurrence Handle1:CAS:528:DC%2BD2MXktVGisw%3D%3D Occurrence Handle10.1016/j.jconrel.2004.09.024

    Article  PubMed  CAS  Google Scholar 

  15. ITP (Invest in Turin and Piedmont). http://www2.polito.it/ricerca/nanotech/Doc/Piemonte/ITP2.pdf (accessed 10/05/05).

  16. N. S. Tambe B. Bhushan (2005) ArticleTitleA new atomic force microscopy based technique for studying nanoscale friction at high sliding velocities J. Phys. D: Appl. Phys. 38 764–773 Occurrence Handle1:CAS:528:DC%2BD2MXis1Sqtr8%3D Occurrence Handle10.1088/0022-3727/38/5/015

    Article  CAS  Google Scholar 

  17. B. Bhushan Z. Burton (2005) ArticleTitleAdhesion and friction properties of polymers in microfluidic devices Nanotechnology 16 467–478 Occurrence Handle1:CAS:528:DC%2BD2MXkvVSrsL4%3D Occurrence Handle10.1088/0957-4484/16/4/023

    Article  CAS  Google Scholar 

  18. B. W. Bequette (2005) ArticleTitleA critical assessment of algorithms and challenges in the development of a closed-loop artificial pancreas Diabetes Technol. Ther. 7 28–47 Occurrence Handle15738702 Occurrence Handle1:CAS:528:DC%2BD2MXhs12qsbc%3D Occurrence Handle10.1089/dia.2005.7.28

    Article  PubMed  CAS  Google Scholar 

  19. H. Ernest and R. Shetty. Impact of nanotechnology on biomedical sciences: review of current concepts on convergence of nanotechnology with biology. http://www.azonano.com/details.asp?ArticleID=1242 (accessed 10/05/05) (May 2005) AZoNano Online J. Nanotechnol. 1:1–14 (2005).

    Google Scholar 

  20. S. Haykin (1998) Neural Networks: A Comprehensive Foundation 2nd ed., Prentice Hall New York

    Google Scholar 

  21. F. E. Ahmed. Artificial neural networks for diagnosis and survival prediction in colon cancer. Mol. Cancer. 4:29–41 (2005).

    Google Scholar 

  22. A. S. Achanta J. G. Kowalski C. T. Rhodes (1995) ArticleTitleArtificial neural networks: implications for pharmaceutical sciences Drug Dev. Ind. Pharm. 21 119–155 Occurrence Handle1:CAS:528:DyaK2MXjtlGmsro%3D

    CAS  Google Scholar 

  23. S. Agatonovic-Kustrin R. Beresford (2000) ArticleTitleBasic concepts of artificial neural network (ANN) modeling and its application in pharmaceutical research J. Pharmaceut. Biomed. Anal. 22 717–727 Occurrence Handle1:CAS:528:DC%2BD3cXisFGqsrY%3D Occurrence Handle10.1016/S0731-7085(99)00272-1

    Article  CAS  Google Scholar 

  24. A. S. Hussain X. Yu R. D. Johnson (1991) ArticleTitleApplication of neural computing in pharmaceutical product development Pharm. Res. 8 1248–1252 Occurrence Handle1796042 Occurrence Handle1:CAS:528:DyaK3MXmtl2murs%3D Occurrence Handle10.1023/A:1015843527138

    Article  PubMed  CAS  Google Scholar 

  25. E. Murtoniemi P. Merkku P. Kinnunen K. Leiviskä J. Yliruusi (1994) ArticleTitleEffect of neural network topology and training end point in modelling the fluidized bed granulation process Int. J. Pharm. 110 101–108 Occurrence Handle1:CAS:528:DyaK2cXlsVWnt78%3D Occurrence Handle10.1016/0378-5173(94)90147-3

    Article  CAS  Google Scholar 

  26. M. Gasperlin L. Tusar M. Tusar J. Kristl J. Smid-Korbar (1998) ArticleTitleLipophilic semisolid emulsion systems: viscoelastic behaviour and prediction of physical stability by neural network modeling Int. J. Pharm. 168 243–254 Occurrence Handle1:CAS:528:DyaK1cXksF2ls7g%3D Occurrence Handle10.1016/S0378-5173(98)00099-4

    Article  CAS  Google Scholar 

  27. K. Takayama M. Fujikawa T. Nagai (1999) ArticleTitleArtificial neural network as a novel method to optimize pharmaceutical formulations Pharm. Res. 16 1–6 Occurrence Handle9950271 Occurrence Handle1:CAS:528:DyaK1MXmtlGntw%3D%3D

    PubMed  CAS  Google Scholar 

  28. J. L. P. Soh F. Chen C. V. Liew D. Shi P. W. S. Heng (2004) ArticleTitleA novel preformulation tool to group microcrystalline celluloses using artificial neural network and data clustering Pharm. Res. 21 2360–2368 Occurrence Handle15648270 Occurrence Handle1:CAS:528:DC%2BD2MXjslyitQ%3D%3D Occurrence Handle10.1007/s11095-004-7690-6

    Article  PubMed  CAS  Google Scholar 

  29. A. Saghatelian B. F. Cravatt (2005) ArticleTitleGlobal strategies to integrate the proteome and metabolome Curr. Opin. Chem. Biol. 9 62–68 Occurrence Handle15701455 Occurrence Handle1:CAS:528:DC%2BD2MXhtV2ksrY%3D Occurrence Handle10.1016/j.cbpa.2004.12.004

    Article  PubMed  CAS  Google Scholar 

  30. J. A. Bilello (2005) ArticleTitleThe agony and ecstasy of “OMIC” technologies in drug development Curr. Mol. Med. 5 39–52 Occurrence Handle15720269 Occurrence Handle1:CAS:528:DC%2BD2MXislOrtbo%3D Occurrence Handle10.2174/1566524053152898

    Article  PubMed  CAS  Google Scholar 

  31. J. K. Nicholson I. D. Wilson (2003) ArticleTitleUnderstanding ‘global’ systems biology: metabonomics and the continuum of metabolism Nat. Rev. Drug Discov. 2 668–676 Occurrence Handle12904817 Occurrence Handle1:CAS:528:DC%2BD3sXmtVGqsbs%3D Occurrence Handle10.1038/nrd1157

    Article  PubMed  CAS  Google Scholar 

  32. S. Portnoy and S. Koepke. Obtaining FDA Approval of Drug/Device Combination Products. Part I: Regulatory Strategy Considerations for Preclinical Testing. http://www.pharmanet-cro.com/pdf/whitepapers/Combo_Products.pdf (accessed 10/05/05), PharmaNet Consulting.

  33. U.S. Food and Drug Administration, Recent Examples of Combination Product Approvals page. http://www.fda.gov/oc/combination/approvals.html (accessed 12/06/05).

  34. U.S. Food and Drug Administration. http://www.fda.gov/nanotechnology/regulation.html (accessed 10/05/05).

  35. N. Sadrieh. FDA perspective on nanomaterial-containing products. ILSI-HESI annual meeting (2005). http://www.fda.gov/nanotechnology/ILSI-HESI-ann-mtg-pres-1-17-05.ppt#1 (accessed 10/05/05).

  36. Definitions. 21 USC 321(h) (1998).

  37. FDA workshop. Innovative systems for delivery of drugs and biologics: scientific, clinical and regulatory challenges, July 8, 2003, Bethesda, MD. http://www.fda.gov/oc/combination/workshop070803.html (accessed 10/05/05).

  38. J. T. Santini SuffixJr. M. J. Cima R. Langer (1999) ArticleTitleA controlled-release microchip Nature 397 335–338 Occurrence Handle9988626 Occurrence Handle1:CAS:528:DyaK1MXhtVyjsLg%3D Occurrence Handle10.1038/16898

    Article  PubMed  CAS  Google Scholar 

  39. J. T. Santini SuffixJr. A. C. Richards R. A. Scheidt M. J. Cima R. Langer (2000) ArticleTitleMicrochips as implantable drug delivery devices Ang. Chem. Int. Ed. 39 2396–2407 Occurrence Handle1:CAS:528:DC%2BD3cXltFCru7s%3D Occurrence Handle10.1002/1521-3773(20000717)39:14<2396::AID-ANIE2396>3.0.CO;2-U

    Article  CAS  Google Scholar 

  40. R. S. Shawgo A. C. R. Grayson Y. Li M. J. Cima (2002) ArticleTitleBioMEMS for drug delivery Curr. Opin. Solid State Mater. Sci. 6 329–334 Occurrence Handle1:CAS:528:DC%2BD38XpsFegtLk%3D Occurrence Handle10.1016/S1359-0286(02)00032-3

    Article  CAS  Google Scholar 

  41. A. C. R Grayson R. S. Shawgo Y. Li M. J. Cima (2004) ArticleTitleElectronic MEMS for triggered delivery Adv. Drug Del. Rev. 56 173–184 Occurrence Handle10.1016/j.addr.2003.07.012 Occurrence Handle1:CAS:528:DC%2BD2cXkvF2jsg%3D%3D

    Article  CAS  Google Scholar 

  42. Y. Li R. S. Shawgo B. Tyler P. T. Henderson J. S. Vogel A. Rosenberg P. B. Storm R. Langer H. Brem M. J. Cima (2004) ArticleTitle Invivo release from a drug delivery MEMS device J. Control. Release 100 211–219 Occurrence Handle15544869 Occurrence Handle1:CAS:528:DC%2BD2cXps1Oru7g%3D Occurrence Handle10.1016/j.jconrel.2004.08.018

    Article  PubMed  CAS  Google Scholar 

  43. Y. Li H. L. H. Duc B. Tyler T. Williams M. Tupper R. Langer H. Brem M. J. Cima (2005) ArticleTitle In vivo delivery of BCNU from a MEMS device to a tumor model J. Control. Release 106 138–145 Occurrence Handle16167384 Occurrence Handle1:CAS:528:DC%2BD2MXntlSiu7w%3D Occurrence Handle10.1016/j.jconrel.2005.04.009

    Article  PubMed  CAS  Google Scholar 

  44. J. M. Maloney, S. A. Uhland, B. F. Polito, N. F. Sheppard Jr., C. M. Pelta, and J. T. Santini Jr. Electrothermally activated microchips for implantable drug delivery and biosensing. J. Control. Release 109:244–255 (2005).

    Google Scholar 

  45. J. H. Prescott S. Lipka S. Baldwin N. F. Sheppard SuffixJr. J. M. Maloney J. Coppeta B. Yomtov M. A. Staples J. T. Santini SuffixJr (2006) ArticleTitleChronic, programmed polypeptide delivery from an implanted, multireservoir microchip device Nat. Biotech. 24 437–438 Occurrence Handle10.1038/nbt1199 Occurrence Handle1:CAS:528:DC%2BD28Xjt1Wisb8%3D

    Article  CAS  Google Scholar 

  46. A. C. R. Grayson I. S. Choi B. M. Tyler P. P. Wang H. Brem M. J. Cima R. Langer (2003) ArticleTitleMulti-pulse drug delivery from a resorbable polymeric microchip device Nat. Mater. 2 767–772 Occurrence Handle1:CAS:528:DC%2BD3sXosFWrtb4%3D Occurrence Handle10.1038/nmat998

    Article  CAS  Google Scholar 

  47. A. C. R. Grayson M. J. Cima R. Langer (2004) ArticleTitleMolecular release from a polymeric microreservoir device: influence of chemistry, polymer swelling, and loading on device performance J. Biomed. Mater. Res. Part A 69A 502–512 Occurrence Handle1:CAS:528:DC%2BD2cXksVyrur8%3D Occurrence Handle10.1002/jbm.a.30019

    Article  CAS  Google Scholar 

  48. A. C. R. Grayson. A Resorbable Polymeric Microreservoir Device for Controlled Release Drug Delivery. Ph.D. thesis, Massachusetts Institute of Technology, 2003.

  49. A. C. R. Grayson G. Voskerician A. Lynn J. M. Anderson M. J. Cima R. Langer (2004) ArticleTitleDifferential degradation rates in vivo and in vitro of biocompatible poly(lactic acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery microchip J. Biomater. Sci., Polym. Ed. 15 1281–1304 Occurrence Handle1:CAS:528:DC%2BD2cXptFait7c%3D Occurrence Handle10.1163/1568562041959991

    Article  CAS  Google Scholar 

  50. ChipRx home page. www.chiprx.com/; also, http://www.chiprx. com/products.html (accessed 10/05/05).

  51. pSividia home page. http://www.psivida.com/ (accessed 10/05/05); BioSilicon™ a novel biomaterial for drug delivery. http://www. psivida.com/docs/fact%20sheets/Drug%20Delivery_190405.pdf (accessed 10/05/05).

  52. Debiotech home page. http://www.debiotech.com/debiotech.html (accessed 10/05/05); DebioSTAR™: an innovative solution for sustained drug delivery.

  53. R. P. Lanza W. L. Chick (1995) ArticleTitleEncapsulated cell therapy Sci.Med. 2 16–25

    Google Scholar 

  54. T. A. Desai D. Hansford M. Ferrari (1999) ArticleTitleCharacterization of micromachined silicon membranes for immunoisolation and bioseparation applications J. Membr. Sci. 159 221–231 Occurrence Handle1:CAS:528:DyaK1MXjtF2juro%3D Occurrence Handle10.1016/S0376-7388(99)00062-9

    Article  CAS  Google Scholar 

  55. F. Lim A. M. Sun (1980) ArticleTitleMicroencapsulated islets as bioartificial endocrine pancreas Science 210 908–910 Occurrence Handle6776628 Occurrence Handle1:CAS:528:DyaL3MXhtlKqsg%3D%3D

    PubMed  CAS  Google Scholar 

  56. M. R. Hoane K. D. Puri L. Xu P. F. Stabila H. Zhao A. G. Gulwadi H. S. Phillips B. Devaux M. D. Lindner W. Tao (2000) ArticleTitleMammalian-cell-produced neurturin (NTN) is more potent than purified Escherichia coli-produced NTN Exp. Neurol. 162 189–193 Occurrence Handle10716899 Occurrence Handle1:CAS:528:DC%2BD3cXhs12hs70%3D Occurrence Handle10.1006/exnr.2000.7311

    Article  PubMed  CAS  Google Scholar 

  57. M. R. Hoane A. G. Gulwadi S. Morrison G. Hovanesian M. D. Lindner W. Tao (1999) ArticleTitleDifferential in vivo effects of neurturin and glial cell-line-derived neurotrophic factor Exp. Neurol. 160 235–243 Occurrence Handle10630208 Occurrence Handle1:CAS:528:DyaK1MXotVOktbk%3D Occurrence Handle10.1006/exnr.1999.7175

    Article  PubMed  CAS  Google Scholar 

  58. W. Tao, R. Wen, M. B. Goddard, S. D. Sherman, P. J. O'Rourke, P. F. Stabila, W. J. Bell, B. J. Dean, K. A. Kauper, V. A. Budz, W. G. Tsiaras, G. M. Acland, S. Pearce-Kelling, A. M. Laties, and G. D. Aguirre. Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. Invest. Ophthalmol. Visual Sci. 43:3292–3298 (2002).

    Google Scholar 

  59. Boston Scientific home page. http://www.bostonscientific.com/ (accessed 10/05/05); Taxus™ stent. http://www.taxus-stent.com/ (accessed 10/05/05).

  60. A. Finkelstein D. McClean S. Kar K. Takizawa K. Varghese N. Baek K. Park M. C. Fishbein R. Makkar F. Litvack N. L. Eigler (2003) ArticleTitleLocal drug delivery via a coronary stent with programmable release pharmacokinetics Circulation 107 777–784 Occurrence Handle12578884 Occurrence Handle10.1161/01.CIR.0000050367.65079.71

    Article  PubMed  Google Scholar 

  61. D. R. McClean N. L. Eigler (2002) ArticleTitleStent design: implications for restenosis Rev. in Cardiovasc. Med. 3 IssueIDSuppl. 5 S16–S22

    Google Scholar 

  62. M. L. Reed C. Wu J. Kneller S. Watkins D. A. Vorp A. Nadeem L. E. Weiss K. Rebello M. Mescher A. J. C. Smith W. Rosenblum M. D. Feldman (1998) ArticleTitleMicromechanical devices for intravascular drug delivery J. Pharm. Sci. 87 1387–1394 Occurrence Handle9811495 Occurrence Handle1:CAS:528:DyaK1cXlvVSrt7k%3D Occurrence Handle10.1021/js980085q

    Article  PubMed  CAS  Google Scholar 

  63. M. L. Reed W.-K. Lye (2004) ArticleTitleMicrosystems for drug and gene delivery Proc. IEEE 92 56–75 Occurrence Handle1:CAS:528:DC%2BD2cXht1eks7g%3D Occurrence Handle10.1109/JPROC.2003.820542

    Article  CAS  Google Scholar 

  64. K. Takahata, A. DeHennis, K. D. Wise, and Y. B. Gianchandani. Stentenna: a micromachined antenna stent for wireless monitoring of implantable microsensors. In Proceedings of the 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society 4:3360–3363 (2003).

  65. J. Hadgraft (2003) Dermal and transdermal delivery M. J. Rathbone J. Hadgraft M. S. Roberts (Eds) Modified Release Drug Delivery Technology Marcel Dekker New York 471–480

    Google Scholar 

  66. M. R. Prausnitz D. E. Ackley J. R. Gyory (2003) Microfabricated microneedles for Transdermal Drug Delivery M. J. Rathbone J. Hadgraft M. S. Roberts (Eds) Modified Release Drug Delivery Technology Marcel Dekker New York 513–522

    Google Scholar 

  67. S. Rajaraman H. T. Henderson (2005) ArticleTitleA unique fabrication approach for microneedles using coherent porous silicon technology Sens. Actuators, B 105 443–448 Occurrence Handle10.1016/j.snb.2004.06.035 Occurrence Handle1:CAS:528:DC%2BD2MXit1anurg%3D

    Article  CAS  Google Scholar 

  68. S. P. Davis B. J. Landis Z. H. Adams M. G. Allen M. R. Prausnitz (2004) ArticleTitleInsertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force J. Biomech. 37 1155–1163 Occurrence Handle15212920 Occurrence Handle10.1016/j.jbiomech.2003.12.010

    Article  PubMed  Google Scholar 

  69. Alza home page. http://www.alza.com/ (accessed 10/05/05); Macroflux® transdermal technology. http://www.alza.com/print/macroflux (accessed 10/05/05).

  70. B. Stoeber D. Liepmann (2005) ArticleTitleArrays of hollow out-of-plane microneedles for drug delivery J. Microelectromech. Syst. 14 472–479 Occurrence Handle10.1109/JMEMS.2005.844843

    Article  Google Scholar 

  71. D. V. McAllister P. M. Wang S. P. Davis J.-H. Park P. J. Canatella M. G. Allen M. R. Prausnitz (2003) ArticleTitleMicrofabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies Proc. Natl. Acad. Sci. USA 100 13755–13760 Occurrence Handle14623977 Occurrence Handle1:CAS:528:DC%2BD3sXpsFGisrw%3D Occurrence Handle10.1073/pnas.2331316100

    Article  PubMed  CAS  Google Scholar 

  72. W. Martanto S. P. Davis N. R. Holiday J. Wang H. S. Gill M. R. Prausnitz (2004) ArticleTitleTransdermal delivery of insulin using microneedles in vivo Pharm. Res. 21 947–952 Occurrence Handle15212158 Occurrence Handle1:CAS:528:DC%2BD2cXktlykurw%3D Occurrence Handle10.1023/B:PHAM.0000029282.44140.2e

    Article  PubMed  CAS  Google Scholar 

  73. H. J. G. E. Gardeniers R. Luttge E. J. W. Berenschot M. J. Boer Particlede S. Y. Yeshurun M. Hefetz R. Oever Particlevan't A. Berg Particlevan den (2003) ArticleTitleSilicon micromachined hollow microneedles for transdermal liquid transport J. Microelectromech. Syst. 12 855–862 Occurrence Handle10.1109/JMEMS.2003.820293

    Article  Google Scholar 

  74. P. Griss G. Stemme (2003) ArticleTitleSide-opened out-of-plane microneedles for microfluidic transdermal liquid transfer J. Microelectromech. Syst. 12 296–301 Occurrence Handle10.1109/JMEMS.2003.809959

    Article  Google Scholar 

  75. A. J. Nijdam A. H. Monica A. P. Gadre J. A. Garra T. J. Long C. Luo M.-C. Cheng T. W. Schneider R. C. White M. Paranjape J. F. Currie (2005) ArticleTitleFluidic encapsulation in SU-8  μ-reservoirs with μ-fluidic through-chip channels Sens. Actuators, A 120 172–183 Occurrence Handle10.1016/j.sna.2004.11.004 Occurrence Handle1:CAS:528:DC%2BD2MXjtlGisrw%3D

    Article  CAS  Google Scholar 

  76. S. Sato C. D. Ebert S. W. Kim (1983) ArticleTitlePrevention of insulin self-association and surface adsorption J. Pharm. Sci. 72 228–232 Occurrence Handle6341536 Occurrence Handle1:CAS:528:DyaL3sXhs1KrtrY%3D

    PubMed  CAS  Google Scholar 

  77. J. R. Brennan S. S. Gebhart W. G. Blackard (1985) ArticleTitlePump-induced insulin aggregation. A problem with the Biostator Diabetes 34 353–359 Occurrence Handle3882499 Occurrence Handle1:CAS:528:DyaL2MXhsl2msbw%3D

    PubMed  CAS  Google Scholar 

  78. M. E. Veen Particlevan der D. G. Iersel Particlevan A. J. Goot Particlevan der R. M. Boom (2004) ArticleTitleShear-induced inactivation of alpha-amylase in a plain shear field Biotechnol. Prog. 20 1140–1145 Occurrence Handle15296441 Occurrence Handle10.1021/bp049976w Occurrence Handle1:CAS:528:DC%2BD2cXjsVSgt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  79. J. C. Wright A. E. Chester R. Skowronski C. Lucas (2003) Long-term controlled delivery of therapeutic agents via an implantable osmotically driven system: The DUROS implant M. J. Rathbone J. Hadgraft M. S. Roberts (Eds) Modified Release Drug Delivery Technology Marcel Dekker New York 657–669

    Google Scholar 

  80. DUROS® Fact Sheet. http://www.durect.com/pdf/duros_fact_ sheet2001.pdf. (accessed 10/05/05).

  81. B. Ziaie A. Baldi M. Lei Y. Gu R. A. Siegel (2004) ArticleTitleHard and soft micromachining for BioMEMS: Review of techniques and examples of applications in microfluidics and drug delivery Adv. Drug Deliv. Rev. 56 145–172 Occurrence Handle14741113 Occurrence Handle1:CAS:528:DC%2BD2cXkvFyquw%3D%3D Occurrence Handle10.1016/j.addr.2003.09.001

    Article  PubMed  CAS  Google Scholar 

  82. A. Baldi Y. Gu P. Loftness R. A. Siegel B. Ziaie (2003) ArticleTitleA hydrogel-actuated environmentally sensitive microvalve for active flow control J. Microelectromech. Syst. 12 613–621 Occurrence Handle10.1109/JMEMS.2003.818070

    Article  Google Scholar 

  83. P. Gravesen J. Branebjerg O. S. Jensen (1993) ArticleTitleMicroFluidics—a review J. Micromech. Microeng. 3 168–182 Occurrence Handle1:CAS:528:DyaK2cXit1WjtLY%3D Occurrence Handle10.1088/0960-1317/3/4/002

    Article  CAS  Google Scholar 

  84. S. Shoji M. Esashi (1994) ArticleTitleMicroflow devices and systems J. Micromech. Microeng. 4 157–171 Occurrence Handle1:CAS:528:DyaK2MXksVKqu7o%3D Occurrence Handle10.1088/0960-1317/4/4/001

    Article  CAS  Google Scholar 

  85. W. L. Benard H. Kahn A. H. Heuer M. A. Huff (1998) ArticleTitleThin-film shape-memory alloy actuated micropumps J. Microelectromech. Syst. 7 245–251 Occurrence Handle1:CAS:528:DyaK1cXjvFSmsLs%3D Occurrence Handle10.1109/84.679390

    Article  CAS  Google Scholar 

  86. D. Maillefer, H. van Lintel, G. Rey-Mermet, and R. Hirschi. A high-performance silicon micropump for an implantable drug delivery system. In Proc. of the 12th IEEE MEMS 1999, pp. 541–546.

  87. D.-S. Lee, C. H. C. Yoon, and J. S. Ko. Fabrication and characterization of a bidirectional valveless peristaltic micropump and its application to a flow-type immunoanalysis. Sens. Actuators, B 103:409–415 (2004).

    Google Scholar 

  88. M. M. Teymoori E. Abbaspour-Sani (2005) ArticleTitleDesign and simulation ofa novel electrostatic peristaltic micromachined pump for drug delivery applications Sens. Actuators, A Phys. 117 222–229 Occurrence Handle10.1016/j.sna.2004.06.025 Occurrence Handle1:CAS:528:DC%2BD2cXotV2gs7s%3D

    Article  CAS  Google Scholar 

  89. L. Cao S. Mantell D. Polla (2001) ArticleTitleDesign and simulation of an implantable medical drug delivery system using microelectromechanical systems technology Sens. Actuators, A 94 117–125 Occurrence Handle10.1016/S0924-4247(01)00680-X

    Article  Google Scholar 

  90. F. J. Martin C. Grove (2001) ArticleTitleMicrofabricated drug delivery systems: concepts to improve clinical benefit Biomed. Microdev. 3 97–108 Occurrence Handle1:CAS:528:DC%2BD3MXms1ehur0%3D Occurrence Handle10.1023/A:1011442024658

    Article  CAS  Google Scholar 

  91. M. Ferrari, P. F. Dehlinger, F. J. Martin, C. F. Grove, and D. R. Friend. Particles for oral delivery of peptides and proteins. USPatent 6,355,270, March 12, 2002.

  92. S. L. Tao T. A. Desai (2003) ArticleTitleMicrofabricated drug delivery systems: from particles to pores Adv. Drug Deliv. Rev. 55 315–328 Occurrence Handle12628319 Occurrence Handle1:CAS:528:DC%2BD3sXhs1Cgur8%3D Occurrence Handle10.1016/S0169-409X(02)00227-2

    Article  PubMed  CAS  Google Scholar 

  93. A. B. Foraker R. J. Walczak M. H. Cohen T. A. Boiarski C. F. Grove P. W. Swann (2003) ArticleTitleMicrofabricated porous silicon particles enhance paracellular delivery of insulin across intestinal Caco-2 cell monolayers Pharm. Res. 20 110–116 Occurrence Handle12608544 Occurrence Handle1:CAS:528:DC%2BD3sXoslKgsg%3D%3D Occurrence Handle10.1023/A:1022211127890

    Article  PubMed  CAS  Google Scholar 

  94. S. L. Tao T. A. Desai (2005) ArticleTitleMicromachined devices: the impact ofcontrolled geometry from cell-targeting to bioavailability J.Control. Rel. 109 127–138 Occurrence Handle1:CAS:528:DC%2BD2MXht12jt7jI Occurrence Handle10.1016/j.jconrel.2005.09.019

    Article  CAS  Google Scholar 

  95. A. Ahmed C. Bonner T. A. Desai (2001) ArticleTitleBioadhesive microdevices for drug delivery: a feasibility study Biomed. Microdev. 3 89–96 Occurrence Handle1:CAS:528:DC%2BD3MXms1ehurw%3D Occurrence Handle10.1023/A:1011489907820

    Article  CAS  Google Scholar 

  96. A. Ahmed C. Bonner T. A. Desai (2002) ArticleTitleBioadhesive microdevices with multiple reservoirs: a new platform for oral drug delivery J. Control. Release 81 291–306 Occurrence Handle12044568 Occurrence Handle1:CAS:528:DC%2BD38XjvFCkur8%3D Occurrence Handle10.1016/S0168-3659(02)00074-3

    Article  PubMed  CAS  Google Scholar 

  97. S. L. Tao M. W. Lubeley T. A. Desai (2003) ArticleTitleBioadhesive poly(methyl methacrylate) microdevices for controlled drug delivery J. Control. Release 88 215–228 Occurrence Handle12628329 Occurrence Handle1:CAS:528:DC%2BD3sXhsFOlsbs%3D Occurrence Handle10.1016/S0168-3659(03)00005-1

    Article  PubMed  CAS  Google Scholar 

  98. A. Heller (2005) ArticleTitleIntegrated medical feedback systems for drug delivery Am. Inst. Chem. Eng. J. 51 1054–1066 Occurrence Handle1:CAS:528:DC%2BD2MXivVGmt74%3D

    CAS  Google Scholar 

  99. P. Brunetti M. O. Federici M. M. Benedetti (2003) ArticleTitleThe artificial pancreas Artif. Cells Blood Substit. Immobil. Biotechnol. 31 127–138 Occurrence Handle12751831 Occurrence Handle10.1081/BIO-120020169

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Norman Sheppard, Jim Prescott and John Santini for their helpful comments during preparation of this review.

Author information

Authors and Affiliations

  1. MicroCHIPS, Inc., 6-B Preston Court, Bedford, Massachusetts, 01730, USA

    Mark Staples

  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Karen Daniel & Robert Langer

  3. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Michael J. Cima

Authors
  1. Mark Staples
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen Daniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. Cima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Staples.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Staples, M., Daniel, K., Cima, M.J. et al. Application of Micro- and Nano-Electromechanical Devices to Drug Delivery. Pharm Res 23, 847–863 (2006). https://doi.org/10.1007/s11095-006-9906-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-006-9906-4

Key Words

Search

Navigation