Transdermal Delivery of Drugs with Microneedles-Potential and Challenges

Kevin Ita, Kevin Ita

Abstract

Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

Keywords: dissolving microneedles; drug delivery; hydrogel-forming microneedles; microneedles; transdermal.

Figures

Figure 1
Figure 1
Different types of microneedles: solid, coated, dissolving and hollow (Reprinted from [14] with permission. Copyright 2012 Elsevier).
Figure 2
Figure 2
Solid microneedles fabricated from silicon, metal and polymer (Reprinted from [14] with permission. Copyright 2012 Elsevier).

References

    1. Lhernould M.S., Deleers M., Delchambre A. Hollow polymer microneedles array resistance and insertion tests. Int. J. Pharm. 2015;480:152–157. doi: 10.1016/j.ijpharm.2015.01.019.
    1. Kim K.S., Ita K., Simon L. Modelling of dissolving microneedles for transdermal drug delivery: theoretical and experimental aspects. Eur. J. Pharm. Sci. 2015;68:137–143. doi: 10.1016/j.ejps.2014.12.008.
    1. Danso M.O., Berkers T., Mieremet A., Hausil F., Bouwstra J.A. An ex vivo human skin model for studying skin barrier repair. Exp. Dermatol. 2015;24:48–54. doi: 10.1111/exd.12579.
    1. Danso M.O., van Drongelen V., Mulder A., Gooris G., van Smeden J., El Ghalbzouri A., Bouwstra J.A. Exploring the potentials of nurture: 2nd and 3rd generation explant human skin equivalents. J. Dermatol. Sci. 2015;77:102–109. doi: 10.1016/j.jdermsci.2014.12.002.
    1. Andrews S.N., Jeong E., Prausnitz M.R. Transdermal delivery of molecules is limited by full epidermis, not just stratum corneum. Pharm. Res. 2013;30:1099–1109. doi: 10.1007/s11095-012-0946-7.
    1. Jepps O.G., Dancik Y., Anissimov Y.G., Roberts M.S. Modeling the human skin barrier—Towards a better understanding of dermal absorption. Adv. Drug Deliv. Rev. 2013;65:152–168. doi: 10.1016/j.addr.2012.04.003.
    1. Flaten G.E., Palac Z., Engesland A., Filipović-Grčić J., Vanić Ž., Škalko-Basnet N. In vitro skin models as a tool in optimization of drug formulation. Eur. J. Pharm. Sci. 2015;75:10–24.
    1. Jacoby E., Jarrahian C., Hull H.F., Zehrung D. Opportunities and challenges in deliveringinfluenza vaccineby microneedle patch. Vaccine. 2015 doi: 10.1016/j.vaccine.2015.03.062.
    1. Chu L.Y., Choi S.O., Prausnitz M.R. Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: Bubble and pedestal microneedle designs. J. Pharm. Sci. 2010;99:4228–4238. doi: 10.1002/jps.22140.
    1. Donnelly R.F., Moffatt K., Alkilani A.Z., Vicente-Pérez E.M., Barry J., McCrudden M.T., Woolfson A.D. Hydrogel-forming microneedle arrays can be effectively inserted in skin by self-application: A pilot study centred on pharmacist intervention and a patient information leaflet. Pharm. Res. 2014;31:1989–1999. doi: 10.1007/s11095-014-1301-y.
    1. Olatunji O., Das D.B., Garland M.J., Belaid L., Donnelly R.F. Influence of array interspacing on the force required for successful microneedle skin penetration: Theoretical and practical approaches. J. Pharm. Sci. 2013;102:1209–1221. doi: 10.1002/jps.23439.
    1. Cheung K., Han T., Das D.B. Effect of Force of Microneedle Insertion on the Permeability of Insulin in Skin. J. Diabetes Sci. Technol. 2014;8:444–452. doi: 10.1177/1932296813519720.
    1. Kaur M., Ita K.B., Popova I.E., Parikh S.J., Bair D.A. Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate. Eur. J. Pharm. Biopharm. 2014;86:284–291. doi: 10.1016/j.ejpb.2013.10.007.
    1. Kim Y.C., Park J.H., Prausnitz M.R. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev. 2012;64:1547–1568. doi: 10.1016/j.addr.2012.04.005.
    1. Verbaan F.J., Bal S.M., van den Berg D.J., Dijksman J.A., van Hecke M., Verpoorten H., van den Berg A., Luttge R., Bouwstra J.A. Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method. J. Control. Release. 2008;128:80–88. doi: 10.1016/j.jconrel.2008.02.009.
    1. Cheung K., Das D.B. Microneedles for drug delivery: Trends and progress. Drug Deliv. 2014 doi: 10.3109/10717544.2014.986309.
    1. Yuzhakov V.V. The AdminPen™ microneedle device for painless & convenient drug delivery. Drug Deliv. Technol. 2010;10:32–36. doi: 10.1016/j.sna.2006.11.022.
    1. Lyon B.J., Aria A.I., Gharib M. Fabrication of carbon nanotube-polyimide composite hollow microneedles for transdermal drug delivery. Biomed. Microdevices. 2014;16:879–886. doi: 10.1007/s10544-014-9892-y.
    1. van der Maaden K., Jiskoot W., Bouwstra J. Microneedle technologies for (trans)dermal drug and vaccine delivery. J. Control. Release. 2012;161:645–655. doi: 10.1016/j.jconrel.2012.01.042.
    1. Gardeniers H.J.G.E., Luttge R., Berenschot E.J.W., de Boer M.J., Yeshurun S.Y., Hefetz M., van’t Oever R., van den Berg A. Silicon micromachined hollow microneedles for transdermal liquid transport. Microelectromech. Syst. 2003;12:855–862. doi: 10.1109/JMEMS.2003.820293.
    1. Perennes F., Marmiroli B., Matteucci M., Tormen M., Vaccari L., Di Fabrizio E. Sharp beveled tip hollow microneedle arrays fabricated by LIGA and 3D soft lithography with polyvinyl alchohol. J. Micromech. Microeng. 2006;16:473–479. doi: 10.1088/0960-1317/16/3/001.
    1. Vinayakumar K.B., Hegde G.M., Nayak M.M., Dinesh N.S., Rajanna K. Fabrication and characterization of gold coated hollow silicon microneedle array for drug delivery. Microelectron. Eng. 2014;128:12–18. doi: 10.1016/j.mee.2014.05.039.
    1. Jun H., Han M.-R., Kang N.-G., Park J.-H., Park J.H. Use of hollow microneedles for targeted delivery of phenylephrine to treat fecal incontinence. J. Control. Release. 2015;207:1–6. doi: 10.1016/j.jconrel.2015.03.031.
    1. Kher G., Trehan S., Misra A. Antisense Oligonucleotides and RNA Interference. In: Misra A., editor. Challenges in Delivery of Therapeutic Genomics and Proteomics. Elsevier; London, UK: 2011. pp. 325–386.
    1. Luo Z., Ye T., Ma Y., Gill H.S., Nitin N. Microprecision delivery of oligonucleotides in a 3D tissue model and its characterization using optical imaging. Mol. Pharm. 2013;10:2868–2879. doi: 10.1021/mp300717f.
    1. Gupta J., Gill H.S., Andrews S.N., Prausnitz M.R. Kinetics of skin resealing after insertion of microneedles in human subjects. J. Control. Release. 2011;154:148–155. doi: 10.1016/j.jconrel.2011.05.021.
    1. Henry S., McAllister D.V., Allen M.G., Prausnitz M.R. Microfabricated microneedles: A novel approach to transdemal drug delivery. J. Pharm. Sci. 1998;87:922–925. doi: 10.1021/js980042+.
    1. Vinayakumar K.B., Hegde G.M., Ramachandra S.G., Nayak M.M., Dinesh N.S., Rajanna K. Development of cup shaped microneedle array for transdermal drug delivery. Biointerphases. 2015;10:021008. doi: 10.1116/1.4919779.
    1. Gill H.S., Prausnitz M.R. Coated microneedles for transdermal delivery. J. Control. Release. 2007;117:227–237. doi: 10.1016/j.jconrel.2006.10.017.
    1. Kim M.-C., Lee J.W., Choi H.-J., Lee Y.-N., Hwang H.S., Lee J., Kim C., Lee J.S., Montemagno C., Prausnitz M.R., et al. Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection. J. Control. Release. 2015;210:208–216. doi: 10.1016/j.jconrel.2015.05.278.
    1. Olatunji O., Igwe C.C., Ahmed A.S., Alhassan D.O.A., Asieba G.O., Das D.B. Microneedles from fish scale biopolymer. J. Appl. Polym. Sci. 2014 doi: 10.1002/app.40377.
    1. Nguyen K.T., Ita K.B., Parikh S.J., Popova I.E., Bair D.A. Transdermal Delivery of Captopril and Metoprolol Tartrate with Microneedles. Drug Deliv. Lett. 2014;4:236–243. doi: 10.2174/2210303104666141001003127.
    1. Nalluri B.N., Sai Sri Anusha V., Sri Bramhini R., Amulya J., Ashraf Sultana S.K., Chandra Teja U., Das D.B. In Vitro Skin Permeation Enhancement of Sumatriptan by Microneedle Application. Curr. Drug Deliv. 2015 doi: 10.2174/1567201812666150304123150.
    1. Edens C., Collins M.L., Goodson J.L., Rota P.A., Prausnitz M.R. A microneedle patch containing measles vaccine is immunogenic in non-human primates. Vaccine. 2015 doi: 10.1016/j.vaccine.2015.02.074. in press.
    1. Wang Q., Yao G., Dong P., Gong Z., Li G., Zhang K., Wu C. Investigation on fabrication process of dissolving microneedle arrays to improve effective needle drug distribution. Eur. J. Pharm. Sci. 2015;66:148–156. doi: 10.1016/j.ejps.2014.09.011.
    1. Sullivan S.P., Koutsonanos D.G., del Pilar Martin M., Lee J.W., Zarnitsyn V., Choi S.-O., Murthy N., Compans R.W., Skountzou I., Prausnitz M.R. Dissolving polymer microneedle patches for influenza vaccination. Nat. Med. 2010;16:915–920. doi: 10.1038/nm.2182.
    1. Hong X., Wei L., Wu F., Wu Z., Chen L., Liu Z., Yuan W. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des. Dev. Ther. 2013:945–952.
    1. Chen M.-C., Huang S.-F., Lai K.-Y., Ling M.-H. Fully embeddable chitosan microneedles as a sustained release depot for intradermal vaccination. Biomaterials. 2013;34:3077–3086. doi: 10.1016/j.biomaterials.2012.12.041.
    1. Lee J.Y., Park S.H., Seo I.H., Lee K.J., Ryu W.H. Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds. Eur. J. Pharm. Biopharm. 2015;94:11–19. doi: 10.1016/j.ejpb.2015.04.024.
    1. Liu S., Jin M., Quan Y., Kamiyama F., Kusamori K., Katsumi H., Sakane T., Yamamoto A. Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin. Eur. J. Pharm. Biopharm. 2013;86:267–276. doi: 10.1016/j.ejpb.2013.10.001.
    1. Chen M.-C., Ling M.-H., Wang K.-W., Lin Z.-W., Lai B.-H., Chen D.-H. Near-infrared light-responsive composite microneedles for on-demand transdermal drug delivery. Biomacromolecules. 2015;16:1598–1607. doi: 10.1021/acs.biomac.5b00185.
    1. Chen H., Zhu H., Zheng J., Mou D., Wan J., Zhang J., Shi T., Zhao Y., Xu H., Yang X. Iontophoresis-driven penetration of nanovesicles through microneedle-induced skin microchannels for enhancing transdermal delivery of insulin. J. Control. Release. 2009;139:63–72. doi: 10.1016/j.jconrel.2009.05.031.
    1. Kim N.W., Lee M.S., Kim K.R., Lee J.E., Lee K., Park J.S., Matsumoto Y., Jo D.-G., Lee H., Lee D.S., et al. Polyplex-releasing microneedles for enhanced cutaneous delivery of DNA vaccine. J. Control. Release. 2014;179:11–17. doi: 10.1016/j.jconrel.2014.01.016.
    1. Pearton M., Saller V., Coulman S.A., Gateley C., Anstey A.V., Zarnitsyn V., Birchall J.C. Microneedle delivery of plasmid DNA to living human skin: Formulation coating, skin insertion and gene expression. J. Control. Release. 2012;160:561–569. doi: 10.1016/j.jconrel.2012.04.005.
    1. Khan H., Mehta P., Msallam H., Armitage D., Ahmad Z. Smart microneedle coatings for controlled delivery and biomedical analysis. J. Drug Target. 2014;22:790–795. doi: 10.3109/1061186X.2014.921926.
    1. Ma Y., Gill H.S. Coating solid dispersions on microneedles via a molten dip-coating method: development and in vitro evaluation for transdermal delivery of a water-insoluble drug. J. Pharm. Sci. 2014;103:3621–3630. doi: 10.1002/jps.24159.
    1. Donnelly R.F., Raj Singh T.R., Alkilani A.Z., McCrudden M.T.C., O’Neill S., O’Mahony C., Armstrong K., McLoone N., Kole P., Woolfson A.D. Hydrogel-forming microneedle arrays exhibit antimicrobial properties: Potential for enhanced patient safety. Int. J. Pharm. 2013;451:76–91. doi: 10.1016/j.ijpharm.2013.04.045.
    1. Donnelly R.F., McCrudden M.T.C., Alkilani A.Z., Larrañeta E., McAlister E., Courtenay A.J., Kearney M.-C., Raj Singh T.R., McCarthy H.O., Kett V.L., et al. Hydrogel-forming microneedles prepared from “super swelling” polymers combined with lyophilised wafers for transdermal drug delivery. PLoS ONE. 2014;9:e111547. doi: 10.1371/journal.pone.0111547.
    1. Donnelly R.F., Mooney K., McCrudden M.T.C., Vicente-Pérez E.M., Belaid L., González-Vázquez P., McElnay J.C., Woolfson A.D. Hydrogel-forming microneedles increase in volume during swelling in skin, but skin barrier function recovery is unaffected. J. Pharm. Sci. 2014;103:1478–1486. doi: 10.1002/jps.23921.
    1. Donnelly R.F., Raj Singh T.R., Garland M.J., Migalska K., Majithiya R., McCrudden C.M., Kole P.L., Tuan-Mahmood T.-M., McCarthy H.O., Woolfson A.D. Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery. Adv. Funct. Mater. 2012;22:4879–4890. doi: 10.1002/adfm.201200864.
    1. Caffarel-Salvador E., Tuan-Mahmood T.-M., McElnay J.C., McCarthy H.O., Mooney K., Woolfson A.D., Donnelly R.F. Potential of hydrogel-forming and dissolving microneedles for use in paediatric populations. Int. J. Pharm. 2015;489:158–169. doi: 10.1016/j.ijpharm.2015.04.076.
    1. Ita K. Transdermal delivery of drugs with microneedles: Strategies and outcomes. J. Drug Deliv. Sci. Technol. 2015;29:16–23. doi: 10.1016/j.jddst.2015.05.001.
    1. Daddona P.E., Matriano J.A., Mandema J., Maa Y.-F. Parathyroid hormone (1–34)-coated microneedle patch system: clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis. Pharm. Res. 2011;28:159–165. doi: 10.1007/s11095-010-0192-9.

Source: PubMed

3
구독하다