Sweat induction using Pilocarpine microneedle patches for sweat testing in healthy adults.

Cystic fibrosis Iontophoresis Microneedle patch Pilocarpine Sweat induction Sweat test

Journal

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966

Informations de publication

Date de publication:
Jan 2024
Historique:
received: 17 01 2023
revised: 17 04 2023
accepted: 19 04 2023
pubmed: 27 5 2023
medline: 27 5 2023
entrez: 26 5 2023
Statut: ppublish

Résumé

The sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities. We created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis. Upon pressing the patch to skin, the MNs dissolve in skin to release pilocarpine for sweat induction. We conducted a non-randomized pilot trial among healthy adults (clinicaltrials.gov, NCT04732195) with pilocarpine and placebo MN patches on one forearm and iontophoresis on the other forearm, followed by sweat collection using Macroduct collectors. Sweat output and sweat chloride concentration were measured. Subjects were monitored for discomfort and skin erythema. Fifty paired sweat tests were conducted in 16 male and 34 female healthy adults. MN patches delivered similar amounts of pilocarpine into skin (1.1 ± 0.4 mg) and induced equivalent sweat output (41.2 ± 25.0 mg) compared to iontophoresis (1.2 ± 0.7 mg and 43.8 ± 32.3 mg respectively). Subjects tolerated the procedure well, with little or no pain, and only mild transient erythema. Sweat chloride concentration measurements in sweat induced by MN patches (31.2 ± 13.4 mmol/L) were higher compared to iontophoresis (24.0 ± 13.2 mmol/L). Possible physiological, methodological, and artifactual causes of this difference are discussed. Pilocarpine MN patches present a promising alternative to iontophoresis to enable increased access to sweat testing for in-clinic and point-of-care applications.

Sections du résumé

BACKGROUND BACKGROUND
The sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities.
METHODS METHODS
We created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis. Upon pressing the patch to skin, the MNs dissolve in skin to release pilocarpine for sweat induction. We conducted a non-randomized pilot trial among healthy adults (clinicaltrials.gov, NCT04732195) with pilocarpine and placebo MN patches on one forearm and iontophoresis on the other forearm, followed by sweat collection using Macroduct collectors. Sweat output and sweat chloride concentration were measured. Subjects were monitored for discomfort and skin erythema.
RESULTS RESULTS
Fifty paired sweat tests were conducted in 16 male and 34 female healthy adults. MN patches delivered similar amounts of pilocarpine into skin (1.1 ± 0.4 mg) and induced equivalent sweat output (41.2 ± 25.0 mg) compared to iontophoresis (1.2 ± 0.7 mg and 43.8 ± 32.3 mg respectively). Subjects tolerated the procedure well, with little or no pain, and only mild transient erythema. Sweat chloride concentration measurements in sweat induced by MN patches (31.2 ± 13.4 mmol/L) were higher compared to iontophoresis (24.0 ± 13.2 mmol/L). Possible physiological, methodological, and artifactual causes of this difference are discussed.
CONCLUSIONS CONCLUSIONS
Pilocarpine MN patches present a promising alternative to iontophoresis to enable increased access to sweat testing for in-clinic and point-of-care applications.

Identifiants

pubmed: 37236899
pii: S1569-1993(23)00120-0
doi: 10.1016/j.jcf.2023.04.014
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT04732195']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

112-119

Informations de copyright

Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interests SL, LG and MRP have submitted a patent application for the use of pilocarpine microneedles for sweat testing (United States Patents and Trademarks Office provisional patent application number 63/132,086 – patent pending). MRP is an inventor of patents, consultant to companies, and founder and shareholder of companies that are developing microneedle patch technologies related to those addressed in this study. This conflict of interest is disclosed and managed by Georgia Tech.

Auteurs

Jonathan Yuxuan Chen (JY)

The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, GA 30332, USA; Global Center for Medical Innovation, Atlanta, GA 30318, USA.

Song Li (S)

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

George L Silva (GL)

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30332, USA; Center for CF & Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

Joshua D Chandler (JD)

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30332, USA; Center for CF & Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

Mark R Prausnitz (MR)

The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, GA 30332, USA; School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: prausnitz@gatech.edu.

Lokesh Guglani (L)

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30332, USA; Center for CF & Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA. Electronic address: lokesh.guglani@emory.edu.

Classifications MeSH