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Home / Equine Research Bank / Bioeng Transl Med / Administration of pilocarpine by microneedle patch as a nove...
Bioengineering & translational medicine2021; 6(3); e10222; doi: 10.1002/btm2.10222

Administration of pilocarpine by microneedle patch as a novel method for cystic fibrosis sweat testing.

Abstract: The sweat test is the gold standard for the diagnosis of cystic fibrosis (CF). The test utilizes iontophoresis to administer pilocarpine to the skin to induce sweating for measurement of chloride concentration in sweat. However, the sweat test procedure needs to be conducted in an accredited lab with dedicated instrumentation, and it can lead to inadequate sweat samples being collected in newborn babies and young children due to variable sweat production with pilocarpine iontophoresis. We tested the feasibility of using microneedle (MN) patches as an alternative to iontophoresis to administer pilocarpine to induce sweating. Pilocarpine-loaded MN patches were developed. Both MN patches and iontophoresis were applied on horses to induce sweating. The sweat was collected to compare the sweat volume and chloride concentration. The patches contained an array of 100 MNs measuring 600 μm long that were made of water-soluble materials encapsulating pilocarpine nitrate. When manually pressed to the skin, the MN patches delivered >0.5 mg/cm pilocarpine, which was double that administered by iontophoresis. When administered to horses, MN patches generated the same volume of sweat when normalized to drug dose and more sweat when normalized to skin area compared to iontophoresis using a commercial device. Moreover, both MN patches and iontophoresis generated sweat with comparable chloride concentration. These results suggest that administration of pilocarpine by MN patches may provide a simpler and more-accessible alternative to iontophoresis for performing a sweat test for the diagnosis of CF.
© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.
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Publication Date: 2021-04-03 PubMed ID: 34589599PubMed Central: PMC8459588DOI: 10.1002/btm2.10222Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research studied a new method for conducting sweat tests in cystic fibrosis (CF) diagnosis, using microneedle (MN) patches to deliver pilocarpine and induce sweating, instead of using the traditional iontophoresis method.

Background

  • The sweat test is a crucial diagnostic tool for identifying cystic fibrosis (CF), a life-threatening genetic disorder.
  • The conventional method involves iontophoresis, a process that uses electricity to administer the drug pilocarpine to the skin, causing it to sweat.
  • The researchers mention that this process often results in inadequate sweat samples, especially with newborn babies and young children due to the variable sweat production.
  • These issues arise from pilocarpine iontophoresis and the need to have the procedure carried out in a specialised lab with dedicated instrumentation.

The New Method

  • The study proposes using microneedle (MN) patches to administer pilocarpine as an alternative to iontophoresis.
  • Microneedle patches were developed and loaded with pilocarpine. Each patch has 100 MNs. Each MN is 600 μm long and is made from water-soluble materials which encapsulate the pilocarpine nitrate.
  • In contrast to iontophoresis, the MN patches deliver more than double the dose of pilocarpine, when manually pressed onto the skin.

Testing and Comparison

  • The researchers tested this new method on horses, and collected the resultant sweat to compare the sweat volume and chloride concentration between iontophoresis and MN patches.
  • Compared to iontophoresis using a commercial device, the MN patches generated an equal volume of sweat when normalized to the drug dose. It also produced more sweat when normalized to skin area.
  • The study also found that both iontophoresis and MN patches generated sweat with comparable chloride concentration, indicating that MN patches could also effectively diagnose CF based on sweat chloride concentration.

Conclusions

  • The use of microneedle patches presents a simpler alternative to iontophoresis in administering pilocarpine for CF sweat testing.
  • The research implies that it might lead to more accessible and easier sweat testing, especially in children where the traditional method often faces difficulties.

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Cite This Article

APA
Li S, Hart K, Norton N, Ryan CA, Guglani L, Prausnitz MR. (2021). Administration of pilocarpine by microneedle patch as a novel method for cystic fibrosis sweat testing. Bioeng Transl Med, 6(3), e10222. https://doi.org/10.1002/btm2.10222

Publication

Bioengineering & translational medicine
ISSN: 2380-6761
NlmUniqueID: 101689146
Country: United States
Language: English
Volume: 6
Issue: 3
Pages: e10222
PII: e10222

Researcher Affiliations

Li, Song
  • School of Chemical and Biomolecular Engineering Georgia Institute of Technology Atlanta Georgia USA.
Hart, Kelsey
  • Department of Large Animal Medicine University of Georgia College of Veterinary Medicine Athens Georgia USA.
Norton, Natalie
  • Department of Large Animal Medicine University of Georgia College of Veterinary Medicine Athens Georgia USA.
Ryan, Clare A
  • Department of Large Animal Medicine University of Georgia College of Veterinary Medicine Athens Georgia USA.
Guglani, Lokesh
  • Center for Cystic Fibrosis and Airways Disease Research Emory University Department of Pediatrics and Children's Healthcare of Atlanta Atlanta Georgia USA.
Prausnitz, Mark R
  • School of Chemical and Biomolecular Engineering Georgia Institute of Technology Atlanta Georgia USA.

Conflict of Interest Statement

M. R. P. is an inventor of patents licensed to companies developing microneedle‐based products, is a paid advisor to companies developing microneedle‐based products, and he is a founder/shareholder of companies developing microneedle‐based products (Micron Biomedical). This potential conflict of interest has been disclosed and is managed by Georgia Tech.

References

This article includes 39 references
  1. Guglani L. Changing the Paradigm - Treating the Basic Defect in Cystic Fibrosis.. Indian J Pediatr 2015 Aug;82(8):727-36.
    doi: 10.1007/s12098-015-1786-3pubmed: 26077199google scholar: lookup
  2. Elborn JS. Cystic fibrosis.. Lancet 2016 Nov 19;388(10059):2519-2531.
    doi: 10.1016/S0140-6736(16)00576-6pubmed: 27140670google scholar: lookup
  3. Coffey MJ, Whitaker V, Gentin N, Junek R, Shalhoub C, Nightingale S, Hilton J, Wiley V, Wilcken B, Gaskin KJ, Ooi CY. Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era.. J Pediatr 2017 Feb;181:137-145.e1.
    doi: 10.1016/j.jpeds.2016.10.045pubmed: 27837951google scholar: lookup
  4. Mishra A, Greaves R, Massie J. The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era.. Clin Biochem Rev 2005 Nov;26(4):135-53.
    pmc: PMC1320177pubmed: 16648884
  5. Kleyn M, Korzeniewski S, Grigorescu V, Young W, Homnick D, Goldstein-Filbrun A, Schuen J, Nasr S. Predictors of insufficient sweat production during confirmatory testing for cystic fibrosis.. Pediatr Pulmonol 2011 Jan;46(1):23-30.
    doi: 10.1002/ppul.21318pubmed: 20812243google scholar: lookup
  6. Eng W, LeGrys VA, Schechter MS, Laughon MM, Barker PM. Sweat-testing in preterm and full-term infants less than 6 weeks of age.. Pediatr Pulmonol 2005 Jul;40(1):64-7.
    doi: 10.1002/ppul.20235pubmed: 15880420google scholar: lookup
  7. LeGrys VA. Sweat testing for cystic fibrosis: profiles of patients with insufficient samples.. Clin Lab Sci 1993 Mar-Apr;6(2):73-4.
    pubmed: 10148584
  8. Moran J, Quirk K, Duff AJ, Brownlee KG. Newborn screening for CF in a regional paediatric centre: the psychosocial effects of false-positive IRT results on parents.. J Cyst Fibros 2007 May;6(3):250-4.
    doi: 10.1016/j.jcf.2006.09.001pubmed: 17056302google scholar: lookup
  9. Hayeems RZ, Miller FA, Barg CJ, Bombard Y, Carroll JC, Tam K, Kerr E, Chakraborty P, Potter BK, Patton S, Bytautas JP, Taylor L, Davies C, Milburn J, Price A, Gonska T, Keenan K, Ratjen F, Guttmann A. Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis.. J Pediatr 2017 May;184:165-171.e1.
    doi: 10.1016/j.jpeds.2017.01.049pubmed: 28279431google scholar: lookup
  10. GIBSON LE, COOKE RE. A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis.. Pediatrics 1959 Mar;23(3):545-9.
    pubmed: 13633369
  11. Prausnitz MR. Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin.. Annu Rev Chem Biomol Eng 2017 Jun 7;8:177-200.
    doi: 10.1146/annurev-chembioeng-060816-101514pubmed: 28375775google scholar: lookup
  12. Kirkby M, Hutton ARJ, Donnelly RF. Microneedle Mediated Transdermal Delivery of Protein, Peptide and Antibody Based Therapeutics: Current Status and Future Considerations.. Pharm Res 2020 Jun 2;37(6):117.
    doi: 10.1007/s11095-020-02844-6pmc: PMC7266419pubmed: 32488611google scholar: lookup
  13. Nguyen TT, Park JH. Human studies with microneedles for evaluation of their efficacy and safety.. Expert Opin Drug Deliv 2018 Mar;15(3):235-245.
    doi: 10.1080/17425247.2018.1410138pubmed: 29169288google scholar: lookup
  14. Duarah S, Sharma M, Wen J. Recent advances in microneedle-based drug delivery: Special emphasis on its use in paediatric population.. Eur J Pharm Biopharm 2019 Mar;136:48-69.
    doi: 10.1016/j.ejpb.2019.01.005pubmed: 30633972google scholar: lookup
  15. Ita K. Dissolving microneedles for transdermal drug delivery: Advances and challenges.. Biomed Pharmacother 2017 Sep;93:1116-1127.
    doi: 10.1016/j.biopha.2017.07.019pubmed: 28738520google scholar: lookup
  16. Leone M, Mönkäre J, Bouwstra JA, Kersten G. Dissolving Microneedle Patches for Dermal Vaccination.. Pharm Res 2017 Nov;34(11):2223-2240.
    doi: 10.1007/s11095-017-2223-2pmc: PMC5643353pubmed: 28718050google scholar: lookup
  17. Vicente-Perez EM, Larrañeta E, McCrudden MTC, Kissenpfennig A, Hegarty S, McCarthy HO, Donnelly RF. Repeat application of microneedles does not alter skin appearance or barrier function and causes no measurable disturbance of serum biomarkers of infection, inflammation or immunity in mice in vivo.. Eur J Pharm Biopharm 2017 Aug;117:400-407.
    doi: 10.1016/j.ejpb.2017.04.029pmc: PMC5496649pubmed: 28478160google scholar: lookup
  18. Arya J, Henry S, Kalluri H, McAllister DV, Pewin WP, Prausnitz MR. Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects.. Biomaterials 2017 Jun;128:1-7.
    doi: 10.1016/j.biomaterials.2017.02.040pmc: PMC5382793pubmed: 28285193google scholar: lookup
  19. Norman JJ, Arya JM, McClain MA, Frew PM, Meltzer MI, Prausnitz MR. Microneedle patches: usability and acceptability for self-vaccination against influenza.. Vaccine 2014 Apr 1;32(16):1856-62.
    doi: 10.1016/j.vaccine.2014.01.076pmc: PMC3979961pubmed: 24530146google scholar: lookup
  20. Rouphael NG, Paine M, Mosley R, Henry S, McAllister DV, Kalluri H, Pewin W, Frew PM, Yu T, Thornburg NJ, Kabbani S, Lai L, Vassilieva EV, Skountzou I, Compans RW, Mulligan MJ, Prausnitz MR. 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 Aug 12;390(10095):649-658.
    doi: 10.1016/S0140-6736(17)30575-5pmc: PMC5578828pubmed: 28666680google scholar: lookup
  21. Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hernandez PA, Sees K, Matriano JA, Gaumer K, Daddona PE. Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women.. J Clin Endocrinol Metab 2010 Jan;95(1):151-8.
    doi: 10.1210/jc.2009-0358pmc: PMC2805490pubmed: 19858319google scholar: lookup
  22. Tepper SJ, Dodick DW, Schmidt PC, Kellerman DJ. Efficacy of ADAM Zolmitriptan for the Acute Treatment of Difficult-to-Treat Migraine Headaches.. Headache 2019 Apr;59(4):509-517.
    doi: 10.1111/head.13482pmc: PMC6590125pubmed: 30698272google scholar: lookup
  23. Daddona PE, Matriano JA, Mandema J, Maa YF. Parathyroid hormone (1-34)-coated microneedle patch system: clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis.. Pharm Res 2011 Jan;28(1):159-65.
    doi: 10.1007/s11095-010-0192-9pubmed: 20567999google scholar: lookup
  24. Fernando GJP, Hickling J, Jayashi Flores CM, Griffin P, Anderson CD, Skinner SR, Davies C, Witham K, Pryor M, Bodle J, Rockman S, Frazer IH, Forster AH. Safety, tolerability, acceptability and immunogenicity of an influenza vaccine delivered to human skin by a novel high-density microprojection array patch (Nanopatch™).. Vaccine 2018 Jun 18;36(26):3779-3788.
    doi: 10.1016/j.vaccine.2018.05.053pubmed: 29779922google scholar: lookup
  25. Ramaut L, Hoeksema H, Pirayesh A, Stillaert F, Monstrey S. Microneedling: Where do we stand now? A systematic review of the literature.. J Plast Reconstr Aesthet Surg 2018 Jan;71(1):1-14.
    doi: 10.1016/j.bjps.2017.06.006pubmed: 28690124google scholar: lookup
  26. Adhikari BB, Goodson JL, Chu SY, Rota PA, Meltzer MI. Assessing the Potential Cost-Effectiveness of Microneedle Patches in Childhood Measles Vaccination Programs: The Case for Further Research and Development.. Drugs R D 2016 Dec;16(4):327-338.
    doi: 10.1007/s40268-016-0144-xpmc: PMC5114202pubmed: 27696306google scholar: lookup
  27. Wing D, Prausnitz MR, Buono MJ. Skin pretreatment with microneedles prior to pilocarpine iontophoresis increases sweat production.. Clin Physiol Funct Imaging 2013 Nov;33(6):436-40.
    doi: 10.1111/cpf.12053pubmed: 23701521google scholar: lookup
  28. Jiang J, Gill HS, Ghate D, McCarey BE, Patel SR, Edelhauser HF, Prausnitz MR. Coated microneedles for drug delivery to the eye.. Invest Ophthalmol Vis Sci 2007 Sep;48(9):4038-43.
    doi: 10.1167/iovs.07-0066pubmed: 17724185google scholar: lookup
  29. Collier RJ, Gebremedhin KG. Thermal biology of domestic animals.. Annu Rev Anim Biosci 2015;3:513-32.
    doi: 10.1146/annurev-animal-022114-110659pubmed: 25387108google scholar: lookup
  30. Hodgson DR, Davis RE, McConaghy FF. Thermoregulation in the horse in response to exercise.. Br Vet J 1994 May-Jun;150(3):219-35.
    doi: 10.1016/s0007-1935(05)80003-xpubmed: 8044664google scholar: lookup
  31. McEwan Jenkinson D, Elder HY, Bovell DL. Equine sweating and anhidrosis Part 1--equine sweating.. Vet Dermatol 2006 Dec;17(6):361-92.
    doi: 10.1111/j.1365-3164.2006.00545.xpubmed: 17083570google scholar: lookup
  32. Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisbury PL 3rd, Tran-Johnson TK, Muscoplat CC, Trivedi M, Goldlust B, Gallagher SC. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group.. Arch Intern Med 1999 Jan 25;159(2):174-81.
    doi: 10.1001/archinte.159.2.174pubmed: 9927101google scholar: lookup
  33. Madeira LG, da Fonseca MA, Fonseca IA, de Oliveira KP, Passos RL, Machado-Moreira CA, Rodrigues LO. Sex-related differences in sweat gland cholinergic sensitivity exist irrespective of differences in aerobic capacity.. Eur J Appl Physiol 2010 May;109(1):93-100.
    doi: 10.1007/s00421-009-1262-8pubmed: 19902243google scholar: lookup
  34. Gill HS, Denson DD, Burris BA, Prausnitz MR. Effect of microneedle design on pain in human volunteers.. Clin J Pain 2008 Sep;24(7):585-94.
    doi: 10.1097/AJP.0b013e31816778f9pmc: PMC2917250pubmed: 18716497google scholar: lookup
  35. Forster AH, Witham K, Depelsenaire ACI, Veitch M, Wells JW, Wheatley A, Pryor M, Lickliter JD, Francis B, Rockman S, Bodle J, Treasure P, Hickling J, Fernando GJP. Safety, tolerability, and immunogenicity of influenza vaccination with a high-density microarray patch: Results from a randomized, controlled phase I clinical trial.. PLoS Med 2020 Mar;17(3):e1003024.
    doi: 10.1371/journal.pmed.1003024pmc: PMC7077342pubmed: 32181756google scholar: lookup
  36. Frew PM, Paine MB, Rouphael N, Schamel J, Chung Y, Mulligan MJ, Prausnitz MR. Acceptability of an inactivated influenza vaccine delivered by microneedle patch: Results from a phase I clinical trial of safety, reactogenicity, and immunogenicity.. Vaccine 2020 Oct 21;38(45):7175-7181.
    doi: 10.1016/j.vaccine.2020.07.064pubmed: 32792250google scholar: lookup
  37. Marshall S, Fleming A, Moore AC, Sahm LJ. Acceptability of microneedle-patch vaccines: A qualitative analysis of the opinions of parents.. Vaccine 2017 Sep 5;35(37):4896-4904.
    doi: 10.1016/j.vaccine.2017.07.083pubmed: 28780122google scholar: lookup
  38. Birchall JC, Clemo R, Anstey A, John DN. Microneedles in clinical practice--an exploratory study into the opinions of healthcare professionals and the public.. Pharm Res 2011 Jan;28(1):95-106.
    doi: 10.1007/s11095-010-0101-2pubmed: 20238152google scholar: lookup
  39. Vassilieva EV, Kalluri H, McAllister D, Taherbhai MT, Esser ES, Pewin WP, Pulit-Penaloza JA, Prausnitz MR, Compans RW, Skountzou I. Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature.. Drug Deliv Transl Res 2015 Aug;5(4):360-71.
    doi: 10.1007/s13346-015-0228-0pmc: PMC4530046pubmed: 25895053google scholar: lookup

Citations

This article has been cited 2 times.
  1. Min J, Tu J, Xu C, Lukas H, Shin S, Yang Y, Solomon SA, Mukasa D, Gao W. Skin-Interfaced Wearable Sweat Sensors for Precision Medicine.. Chem Rev 2023 Apr 26;123(8):5049-5138.
    doi: 10.1021/acs.chemrev.2c00823pubmed: 36971504google scholar: lookup
  2. Ibrahim NFA, Sabani N, Johari S, Manaf AA, Wahab AA, Zakaria Z, Noor AM. A Comprehensive Review of the Recent Developments in Wearable Sweat-Sensing Devices.. Sensors (Basel) 2022 Oct 10;22(19).
    doi: 10.3390/s22197670pubmed: 36236769google scholar: lookup
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