A Perspective on Microneedle-Based Drug Delivery and Diagnostics in Paediatrics

Liliana R Pires, K B Vinayakumar, Maria Turos, Verónica Miguel, João Gaspar, Liliana R Pires, K B Vinayakumar, Maria Turos, Verónica Miguel, João Gaspar

Abstract

Microneedles (MNs) have been extensively explored in the literature as a means to deliver drugs in the skin, surpassing the stratum corneum permeability barrier. MNs are potentially easy to produce and may allow the self-administration of drugs without causing pain or bleeding. More recently, MNs have been investigated to collect/assess the interstitial fluid in order to monitor or detect specific biomarkers. The integration of these two concepts in closed-loop devices holds the promise of automated and minimally invasive disease detection/monitoring and therapy. These assure low invasiveness and, importantly, open a window of opportunity for the application of population-specific and personalised therapies.

Keywords: medical devices; microneedles; paediatrics.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Typical cross section of adult skin and infant skin [19]. (B) Proposal for the potential microneedle application in paediatrics. (C) Microneedle-based diagnostics to monitor the required analyte; microneedles are used to sample the interstitial fluid in a painless manner [13].
Figure 2
Figure 2
(A) Different microneedle architectures used to deliver drugs and to sample interstitial fluid. Scanning electron microscopy micrographs of (1) cup-shaped MNs [33], (2) groove-shaped MNs [34], (3) pocketed MNs [31] and (4) hollow MNs [41]. Fluorescence microscopy images of (5) polymer MNs [42] and (6) fast-dissolving polymeric MNs [43]. (7) Optical coherence tomography images of hydrogel MN following insertion into excised neonatal porcine skin [18]. (B) Schematic shows the microneedle-based approach towards continuous monitoring and drug delivery as a potential closed-loop device.

References

    1. Prausnitz M.R. Microneedles for transdermal drug delivery. Adv. Drug Deliv. Rev. 2004;56:581–587. doi: 10.1016/j.addr.2003.10.023.
    1. Larraneta E., Lutton R.E.M., Woolfson A.D., Donnelly R.F. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater. Sci. Eng. R Rep. 2016;104:1–32. doi: 10.1016/j.mser.2016.03.001.
    1. Peng W.K., Paesani D. Omics Meeting Onics: Towards the Next Generation of Spectroscopic-Based Technologies in Personalized Medicine. J. Pers. Med. 2019;9:39. doi: 10.3390/jpm9030039.
    1. Wang M., Hu L.Z., Xu C.J. Recent advances in the design of polymeric microneedles for transdermal drug delivery and biosensing. Lab Chip. 2017;17:1373–1387. doi: 10.1039/C7LC00016B.
    1. Chiappini C. Nanoneedle-Based Sensing in Biological Systems. ACS Sens. 2017;2:1086–1102. doi: 10.1021/acssensors.7b00350.
    1. . [(accessed on 1 October 2019)]; Available online: .
    1. Rouphael N.G., Paine M., Mosley R., Henry S., McAllister D.V., Kalluri H., Pewin W., Frew P.M., Yu T.W., Thornburg N.J., et al. The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): A randomised, partly blinded, placebo-controlled, phase 1 trial. Lancet. 2017;390:649–658. doi: 10.1016/S0140-6736(17)30575-5.
    1. Troy S.B., Kouiavskaia D., Siik J., Kochba E., Beydoun H., Mirochnitchenko O., Levin Y., Khardori N., Chumakov K., Maldonado Y. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults. J. Infect. Dis. 2015;211:1969–1976. doi: 10.1093/infdis/jiu841.
    1. Bhatnagar S., Saju A., Cheerla K.D., Gade S.K., Garg P., Venuganti V.V.K. Corneal delivery of besifloxacin using rapidly dissolving polymeric microneedles. Drug Deliv. Transl. Res. 2018;8:473–483. doi: 10.1007/s13346-017-0470-8.
    1. Ma Y., Tao W., Krebs S.J., Sutton W.F., Haigwood N.L., Gill H.S. Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity. Pharm. Res. 2014;31:2393–2403. doi: 10.1007/s11095-014-1335-1.
    1. Wang N., Zhen Y., Jin Y., Wang X., Li N., Jiang S., Wang T. Combining different types of multifunctional liposomes loaded with ammonium bicarbonate to fabricate microneedle arrays as a vaginal mucosal vaccine adjuvant-dual delivery system (VADDS) J. Control. Release. 2017;246:12–29. doi: 10.1016/j.jconrel.2016.12.009.
    1. Lee J., Kim D.H., Lee K.J., Seo I.H., Park S.H., Jang E.H., Park Y., Youn Y.N., Ryu W. Transfer-molded wrappable microneedle meshes for perivascular drug delivery. J. Control. Release. 2017;268:237–246. doi: 10.1016/j.jconrel.2017.10.007.
    1. Chua B., Desai S.P., Tierney M.J., Tamada J.A., Jina A.N. Effect of microneedles shape on skin penetration and minimally invasive continuous glucose monitoring in vivo. Sens. Actuators A Phys. 2013;203:373–381. doi: 10.1016/j.sna.2013.09.026.
    1. Mooney K., McElnay J.C., Donnelly R.F. Children’s views on microneedle use as an alternative to blood sampling for patient monitoring. Int. J. Pharm. Pract. 2014;22:335–344. doi: 10.1111/ijpp.12081.
    1. Teunissen M.B.M., Haniffa M., Collin M.P. Insight into the Immunobiology of Human Skin and Functional Specialization of Skin Dendritic Cell Subsets to Innovate Intradermal Vaccination Design. In: Teunissen M.B.M., editor. Intradermal Immunization. Volume 351. Springer-Verlag Berlin; Berlin, Germany: 2012. pp. 25–76.
    1. Schipper P., van der Maaden K., Groeneveld V., Ruigrok M., Romeijn S., Uleman S., Oomens C., Kersten G., Jiskoot W., Bouwstra J. Diphtheria toxoid and N-trimethyl chitosan layer-by-layer coated pH-sensitive microneedles induce potent immune responses upon dermal vaccination in mice. J. Control. Release. 2017;262:28–36. doi: 10.1016/j.jconrel.2017.07.017.
    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. 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. Duarah S., Sharma M., Wen J.Y. Recent advances in microneedle-based drug delivery: Special emphasis on its use in paediatric population. Eur. J. Pharm. Biopharm. 2019;136:48–69. doi: 10.1016/j.ejpb.2019.01.005.
    1. Tollefson M., Siegel D. Advancing paediatric psoriasis treatment options for children. Br. J. Dermatol. 2017;177:1470–1471. doi: 10.1111/bjd.16026.
    1. Waghule T., Singhvi G., Dubey S.K., Pandey M.M., Gupta G., Singh M., Dua K. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomed. Pharmacother. 2019;109:1249–1258. doi: 10.1016/j.biopha.2018.10.078.
    1. Ameri M., Kadkhodayan M., Nguyen J., Bravo J.A., Su R., Chan K., Samiee A., Daddona P.E. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses. Pharmaceutics. 2014;6:220–234. doi: 10.3390/pharmaceutics6020220.
    1. Ferrante G., La Grutta S. The Burden of Pediatric Asthma. Front. Pediatr. 2018;6 doi: 10.3389/fped.2018.00186.
    1. Shakya A.K., Lee C.H., Gill H.S. Coated microneedle-based cutaneous immunotherapy prevents Der p 1-induced airway allergy in mice. J. Allergy Clin. Immunol. 2018;142:2007–2011. doi: 10.1016/j.jaci.2018.08.017.
    1. American Diabetes Association . [(accessed on 1 October 2019)]; Available online: .
    1. Jin X., Zhu D.D., Chen B.Z., Ashfaq M., Guo X.D. Insulin delivery systems combined with microneedle technology. Adv. Drug Deliv. Rev. 2018;127:119–137. doi: 10.1016/j.addr.2018.03.011.
    1. Jina A., Tierney M.J., Tamada J.A., McGill S., Desai S., Chua B., Chang A., Christiansen M. Design, development, and evaluation of a novel microneedle array-based continuous glucose monitor. J. Diabetes Sci. Technol. 2014;8:483–487. doi: 10.1177/1932296814526191.
    1. Sharma S., El-Laboudi A., Reddy M., Jugnee N., Sivasubramaniyam S., El Sharkawy M., Georgiou P., Johnston D., Oliver N., Cass A.E.G. A pilot study in humans of microneedle sensor arrays for continuous glucose monitoring. Anal. Methods. 2018;10:2088–2095. doi: 10.1039/C8AY00264A.
    1. Lee H., Choi T.K., Lee Y.B., Cho H.R., Ghaffari R., Wang L., Choi H.J., Chung T.D., Lu N., Hyeon T., et al. A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. Nat. Nanotechnol. 2016;11:566–572. doi: 10.1038/nnano.2016.38.
    1. Lee H., Song C., Hong Y.S., Kim M.S., Cho H.R., Kang T., Shin K., Choi S.H., Hyeon T., Kim D.H. Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module. Sci. Adv. 2017;3 doi: 10.1126/sciadv.1601314.
    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. Ullah A., Kim C.M., Kim G.M. Porous polymer coatings on metal microneedles for enhanced drug delivery. R. Soc. Open Sci. 2018;5 doi: 10.1098/rsos.171609.
    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 doi: 10.1116/1.4919779.
    1. Han M., Kim D.K., Kang S.H., Yoon H.R., Kim B.Y., Lee S.S., Kim K.D., Lee H.G. Improvement in antigen-delivery using fabrication of a grooves-embedded microneedle array. Sens. Actuators B Chem. 2009;137:274–280. doi: 10.1016/j.snb.2008.11.017.
    1. Amodwala S., Kumar P., Thakkar H.P. Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis. Eur. J. Pharm. Sci. 2017;104:114–123. doi: 10.1016/j.ejps.2017.04.001.
    1. Martin C.J., Allender C.J., Brain K.R., Morrissey A., Birchall J.C. Low temperature fabrication of biodegradable sugar glass microneedles for transdermal drug delivery applications. J. Control. Release. 2012;158:93–101. doi: 10.1016/j.jconrel.2011.10.024.
    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. Walsh L., Ryu J., Bock S., Koval M., Mauro T., Ross R., Desai T. Nanotopography Facilitates in Vivo Transdermal Delivery of High Molecular Weight Therapeutics through an Integrin-Dependent Mechanism. Nano Lett. 2015;15:2434–2441. doi: 10.1021/nl504829f.
    1. Chang H., Zheng M., Yu X., Than A., Seeni R.Z., Kang R., Tian J., Khanh D.P., Liu L., Chen P., et al. A Swellable Microneedle Patch to Rapidly Extract Skin Interstitial Fluid for Timely Metabolic Analysis. Adv. Mater. 2017;29:1702243. doi: 10.1002/adma.201702243.
    1. Li C.G., Joung H.-A., Noh H., Song M.-B., Kim M.-G., Jung H. One-touch-activated blood multidiagnostic system using a minimally invasive hollow microneedle integrated with a paper-based sensor. Lab Chip. 2015;15:3286–3292. doi: 10.1039/C5LC00669D.
    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. Demuth P.C., Min Y., Irvine D.J., Hammond P.T. Implantable silk composite microneedles for programmable vaccine release kinetics and enhanced immunogenicity in transcutaneous immunization. Adv. Healthc. Mater. 2014;3:47–58. doi: 10.1002/adhm.201300139.
    1. Pan J.T., Ruan W.Y., Qin M.Y., Long Y.M., Wan T., Yu K.Y., Zhai Y.H., Wu C.B., Xu Y.H. Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving microneedles. Sci. Rep. 2018;8:11. doi: 10.1038/s41598-018-19463-2.
    1. Zhu Z.H., Liu T., Li G.Y., Li T., Inoue Y. Wearable Sensor Systems for Infants. Sensors. 2015;15:3721–3749. doi: 10.3390/s150203721.
    1. Kim J., Campbell A.S., de Avila B.E.F., Wang J. Wearable biosensors for healthcare monitoring. Nat. Biotechnol. 2019;37:389–406. doi: 10.1038/s41587-019-0045-y.
    1. Vinayakumar K.B., Kulkarni P.G., Nayak M.M., Dinesh N.S., Hegde G.M., Ramachandra S.G., Rajanna K. A hollow stainless steel microneedle array to deliver insulin to a diabetic rat. J. Micromech. Microeng. 2016;26 doi: 10.1088/0960-1317/26/6/065013.
    1. Vinayakumar K.B., Nadiger G., Shetty V.R., Dinesh N.S., Nayak M.M., Rajanna K. Packaged peristaltic micropump for controlled drug delivery application. Rev. Sci. Instrum. 2017;88 doi: 10.1063/1.4973513.
    1. Cobo A., Sheybani R., Meng E. MEMS: Enabled Drug Delivery Systems. Adv. Healthc. Mater. 2015;4:969–982. doi: 10.1002/adhm.201400772.
    1. Lee H.J., Choi N., Yoon E.S., Cho I.J. MEMS devices for drug delivery. Adv. Drug Deliv. Rev. 2018;128:132–147. doi: 10.1016/j.addr.2017.11.003.

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