Solid silicon microneedles for drug delivery applications

  • S. Pradeep Narayanan
  • S. Raghavan


In this work, solid silicon (Si) microneedles with a higher aspect ratio and sharper tips are fabricated. Tetramethylammonium Hydroxide (TMAH) etching factors have been optimized and used to fabricate long and tapered microneedles. The needles thus fabricated are found to be suitable for transdermal drug delivery applications. The optimized etching factors include varying the concentration of TMAH, etching time, etching rates, temperature, and window size of optical mask. It is found that by increasing the window size, the etch rates in both vertical and lateral directions increase extensively. However, on increasing the temperature beyond 90 °C, etching becomes rapid and uncontrollable. In order to obtain microneedles with high aspect ratio, sample placement in the glass boat of TMAH setup and TMAH concentration should be manipulated to attain a higher etch rate in vertical direction compared to the lateral one. Solid silicon microneedles with an average height of 158 μm, base width of 110.5 μm, aspect ratio of 1.43, tip angle of 19.4° and tip diameter of 0.40 μm are successfully fabricated. A microhardness value of 44.4 (HRC) was obtained for the fabricated Si microneedles. This is 52.2 times higher than the skin Ultimate Tensile Strength (UTS), which makes insertion of microneedles through the skin safer and easier without any breakage.


Bio-MEMS Drug delivery Silicon microneedles Transdermal patch 


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  1. 1.
    Prausnitz MR (2004) Microneedles for transdermal drug delivery. Adv Drug Deliv Rev 56:581–587CrossRefGoogle Scholar
  2. 2.
    Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nat Biotechnol 26:1261–1268CrossRefGoogle Scholar
  3. 3.
    Guy RH, Hadgraft J (2003) Transdermal Drug Delivery. Marcel Dekker, New YorkGoogle Scholar
  4. 4.
    Williams A (2003) Transdermal and topical drug delivery. Pharmaceutical Press, LondonGoogle Scholar
  5. 5.
    Prausnitz MR, Mitragotri S, Langer R (2004) Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov 3:115–124CrossRefGoogle Scholar
  6. 6.
    Henry S, McAllister DV, Allen MG, Prausnitz MR (1998) Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci 87:922–925CrossRefGoogle Scholar
  7. 7.
    Lin L, Pisano AP (1999) Silicon-processed microneedles. IEEE J Microelectromech Syst 8:78–84CrossRefGoogle Scholar
  8. 8.
    Tao SL, Desai TA (2003) Microfabricated drug delivery systems: from particles to pores. Adv Drug Deliv Rev 55:315–328CrossRefGoogle Scholar
  9. 9.
    McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, Prausnitz MR (2003) Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A 100:13755–13760CrossRefGoogle Scholar
  10. 10.
    Van der maaden K, Sekerdag E, Schipper P, Kersten G, Jiskoot W, Bouwstra J (2015) Layer-by-layer assembly of inactivated poliovirus and N-Trimethyl chitosan on pH-sensitive microneedles for dermal vaccination. Langmuir 31:8654–8660CrossRefGoogle Scholar
  11. 11.
    Quan FS, Kim YC, Song JM, Hwang HS, Compans RW, Prausnitz MR (2013) Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch. Clin Vaccine Immunol 20:1433–1439CrossRefGoogle Scholar
  12. 12.
    Van der maaden K, Jiskoot W, Bouwstra J (2012) Microneedle technologies for (trans) dermal drug and vaccine delivery. J Control Release 161:645–655CrossRefGoogle Scholar
  13. 13.
    Cormier M, Johnson B, Ameri M, Nyam K, Libiran L, Zhang DD, Daddona P (2004) Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release 97:503–511CrossRefGoogle Scholar
  14. 14.
    Park JH, Allen MG, Prausnitz MR (2005) Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release 104:51–66CrossRefGoogle Scholar
  15. 15.
    Martanto W, Moore JS, Kashlan O, Kamath R, Wang PM, O’Neal JM, Prausnitz MR (2006) Microinfusion using hollow microneedles. Pharm Res 23:104–113CrossRefGoogle Scholar
  16. 16.
    Bariya SH, Gohel MC, Mehta TA, Sharma OP (2012) Microneedles: an emerging transdermal drug delivery system. J Pharm Pharmacol 64:11–29CrossRefGoogle Scholar
  17. 17.
    Van der maaden K, Luttge R, Vos PJ, Bouwstra J, Kersten G, Ploemen I (2015) Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays. Drug Deliv and Transl Res 5:397–406CrossRefGoogle Scholar
  18. 18.
    McAllister DV, Allen MG, Prausnitz MR (2000) Microfabricated microneedles for gene and drug delivery. Annu Rev Biomed Eng 2:289–313CrossRefGoogle Scholar
  19. 19.
    Donnelly RF, Singh TRR, Woolfson AD (2010) Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv 17:187–207CrossRefGoogle Scholar
  20. 20.
    Kim YC, Park JH, Prausnitz MR (2012) Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev 64:1547–1568CrossRefGoogle Scholar
  21. 21.
    Pradeep Narayanan S, Raghavan S (2016) Transdermal drug delivery with tiny (micro) needles—an overview. South Asian Journal of Research in Engineering Science and Technology 1:378–387Google Scholar
  22. 22.
    Gill HS, Prausnitz MR (2007) Coated microneedles for transdermal delivery. J Control Release 117:227–237CrossRefGoogle Scholar
  23. 23.
    Vrdoljak A, McGrath MG, Carey JB, Draper SJ, Hill AVS, O’Mahony C, Crean AM, Moore AC (2012) Coated microneedle arrays for transcutaneous delivery of live virus vaccines. J Control Release 159:34–42CrossRefGoogle Scholar
  24. 24.
    Hegde NR, Kaveri SV, Bayry J (2011) Recent advances in the administration of vaccines for infectious diseases: microneedles as painless delivery devices for mass vaccination. Drug Discov Today 16:1061–1068CrossRefGoogle Scholar
  25. 25.
    Cha KJ, Kim T, Park SJ, Kim DS (2014) Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles. J Micromech Microeng 24:115015–115022CrossRefGoogle Scholar
  26. 26.
    Hong X, Wei L, Wu F, Wu Z, Chen L, Liu Z, Yuan W (2013) Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des Deve Ther 7:945–952Google Scholar
  27. 27.
    LaVan DA, McGuire T, Langer R (2003) Small-scale systems for in vivo drug delivery. Nat Biotechnol 21:1184–1191CrossRefGoogle Scholar
  28. 28.
    Hashmi S, Ling P, Hashmi G, Reed M, Gaugler R, Timmer W (1995) Genetic transformation of nematodes using arrays of micromechanical piercing structures. BioTechniques 19:766–770Google Scholar
  29. 29.
    Kaushik S, Hord AH, Denson DD, McAllister DV, Smitra S, Allen MG, Prausnitz MR (2001) Lack of pain associated with Microfabricated microneedles. Anesth Analg 92:502–504CrossRefGoogle Scholar
  30. 30.
    Indermun S, Luttge R, Choonara YE, Kumar P, Toit LCD, Modi G, Pillay V (2014) Current advances in the fabrication of microneedles for transdermal delivery. J Control Release 185:130–138CrossRefGoogle Scholar
  31. 31.
    Mikszta JA, Alarcon JB, Brittingham JM, Sutter DE, Pettis RJ, Harvey NG (2002) Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nat Med 8:415–419CrossRefGoogle Scholar
  32. 32.
    Martanto W, Davis SP, Holiday NR, Wang J, Gill HS, Prausnitz MR (2004) Transdermal delivery of insulin using microneedles in vivo. Pharm Res 21:947–952CrossRefGoogle Scholar
  33. 33.
    Park JH, Choi SO, Seo S, Choy YB, Prausnitz MR (2010) A microneedle roller for transdermal drug delivery. Eur J Pharm Biopharm 76:282–289CrossRefGoogle Scholar
  34. 34.
    Hamzah AA, Aziz NA, Majlis BY, Yunas J, Dee CF, Bais B (2012) Optimization of HNA etching parameters to produce high aspect ratio solid silicon microneedles. J Micromech Microeng 22:095017 (10pp)CrossRefGoogle Scholar
  35. 35.
    Li WZ, Huo MR, Zhou JP, Zhou YQ, Hao BH, Liu T, Zhang Y (2010) Super-short solid silicon microneedles for transdermal drug delivery applications. Int J Pharm 389:122–129CrossRefGoogle Scholar
  36. 36.
    Gill HS, Denson DD, Burris BA, Prausnitz MR (2008) Effect of microneedle design on pain in human subjects. Clin J Pain 24:585–594CrossRefGoogle Scholar
  37. 37.
    Ji J, Tay FEH, Miao J, Iliescu C (2006) Microfabricated microneedle with porous tip for drug delivery. J Micromech Microeng 16:958–964CrossRefGoogle Scholar
  38. 38.
    Wilke N, Hibert C, O’Brien J, Morrissey A (2005) Silicon microneedle electrode array with temperature monitoring for electroporation. Sens Actuators A Phys 123–124:319–325CrossRefGoogle Scholar
  39. 39.
    Hanein Y, Schabmueller CGJ, Holman G, Lucke P, Denton DD, Bohringer KF (2003) High-aspect ratio submicrometer needles for intracellular applications. J Micromech Microeng 13:S91–S95CrossRefGoogle Scholar
  40. 40.
    Lee JW, Park JH, Prausnitz MR (2008) Dissolving microneedles for transdermal drug delivery. Biomaterials 29:2113–2124CrossRefGoogle Scholar
  41. 41.
    Chu LY, Choi SO, Prausnitz MR (2010) Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: bubble and pedestal microneedle designs. J Pharm Sci 99:4228–4238CrossRefGoogle Scholar
  42. 42.
    Sullivan SP, Koutsonanos DG, Martin MDP, Lee JW, Zarnitsyn V, Choi SO, Murthy N, Compans RW, Skountouz I, Prausnitz MR (2010) Dissolving polymer microneedle patches for influenza vaccination. Nat Med 16:915–920CrossRefGoogle Scholar
  43. 43.
    Migalska K, Morrow DIJ, Garland MJ, Thakur R, Woolfson AD, Donelly RF (2011) Laser-engineered dissolving microneedle arrays for transdermal macromolecular drug delivery. Pharm Res 28:1919–1930CrossRefGoogle Scholar
  44. 44.
    Garland MJ, Salvador EC, Migalska K, Woolfson AD, Donelly RF (2012) Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery. J Control Release 159:52–59CrossRefGoogle Scholar
  45. 45.
    McCrudden MTC, Alkilani AZ, McCrudden CM, McAlister E, McCarthy HO, Woolfson AD, Donelly RF (2014) Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs. J Control Release 180:71–80CrossRefGoogle Scholar
  46. 46.
    Lahiji SF, Dangol M, Jung H (2015) A patchless dissolving microneedle delivery system enabling rapid and efficient transdermal drug delivery. Sci Rep 5:7914 (1–7)CrossRefGoogle Scholar
  47. 47.
    Mistilis MJ, Joyce JC, Esser ES, Skountouz I, Compans RW, Bommarius AS, Prausnitz MR (2016) Long-term stability of influenza vaccine in a dissolving microneedle patch. Drug Deliv and Transl Res. doi: 10.1007/s13346-016-0282-2 Google Scholar
  48. 48.
    Chen YT, Hsu CC, Tsai CH, Kang SW (2010) Fabrication of microneedles. J Mar Sci Tech Taiw 18:243–248Google Scholar
  49. 49.
    Music S, Vincekovic NF, Sekovanic L (2011) Precipitation of amorphous SiO2 particles and their properties. Braz J Chem Eng 28:89–94CrossRefGoogle Scholar
  50. 50.
    Matsui Y, Adachi S (2012) Optical properties of porous silicon layers formed by Electroless photovoltaic etching. ECS J Solid State Sci Technol 1:R80–R85CrossRefGoogle Scholar
  51. 51.
    Oliver WC, Pharr GM (1992) An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res 7:1564–1583CrossRefGoogle Scholar
  52. 52.
    Sakharova NA, Fernandes JV, Antunes JM, Oliveira MC (2009) Comparison between Berkovich, Vickers and conical indentation tests: a three-dimensional numerical simulation study. Int J Solids Struct 46:1095–1104CrossRefMATHGoogle Scholar
  53. 53.
    Gallagher AJ, Anniadh AN, Bruyere K, Otténio M, Xie H, Gilchrist MD (2012) Dynamic tensile properties of human skin. IRCOBI Conference 59:494–502Google Scholar
  54. 54.
    Metrics M Accessed 18 August 2016

Copyright information

© Springer-Verlag London 2016

Authors and Affiliations

  1. 1.Department of Electronics and Communication EngineeringNational Institute of TechnologyTiruchirappalliIndia

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