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

• Published in: Journal of cystic fibrosis Vol. 23; no. 1; pp. 112 - 119
• Main Authors: Chen, Jonathan Yuxuan, Li, Song, Silva, George L., Chandler, Joshua D., Prausnitz, Mark R., Guglani, Lokesh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2024
• Subjects: Adult; Child; Child, Preschool; Chlorides; Cystic fibrosis; Cystic Fibrosis - diagnosis; Erythema; Female; Humans; Infant; Iontophoresis; Male; Microneedle patch; Pilocarpine; Pulmonary/Respiratory; Reproducibility of Results; Sweat; Sweat induction; Sweat test; Iontophoresis; Cystic fibrosis; Pilocarpine; Sweat test; Sweat induction; Microneedle patch
• ISSN: 1569-1993; 1873-5010; 1873-5010
• DOI: 10.1016/j.jcf.2023.04.014

•Dissolvable microneedle patches loaded with pilocarpine nitrate were developed to induce sweating in healthy adults for screening of cystic fibrosis.•Microneedle patch-based delivery of pilocarpine nitrate delivered pilocarpine and induced sweating similar to iontophoresis delivery.•Microneedle patches were well tolerated and more preferred by subjects compared to conventional iontophoresis.•Chloride concentration measurements in sweat induced by microneedle patches were elevated compared to sweat induced by iontophoresis. 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.