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/cm2 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.

Skin-Interfaced Wearable Sweat Sensors for Precision Medicine

“…Moreover, periodic iontophoresis of different acetylcholine loads was performed and higher sweat rate with longer sweat duration was observed for the 10% acetylcholine gel compared to the 1% acetylcholine gel (Figure c). In addition to the gel-based wearable systems, ,,− a pilocarpine-loaded microneedle patch was recently developed for sweat testing . With an array of 100 microneedles at a length of 600 μm, the iontophoresis patch is much smaller and thinner than a regular commercial iontophoresis gel (Figure d).…”

“…d – f , A microneedle-based iontophoresis device ( d ) and in vivo sweat responses of the device ( e,f ). Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Wiley.…”

“…In addition to the gelbased wearable systems, 190,254,328−331 a pilocarpine-loaded microneedle patch was recently developed for sweat testing. 327 With an array of 100 microneedles at a length of 600 μm, the iontophoresis patch is much smaller and thinner than a regular commercial iontophoresis gel (Figure 15d). In an equine model, the microneedle patch produces a much higher sweating volume per unit area and unit dose compared to the pilocarpine hydrogel (Figure 15e,f).…”

Access and Management of Sweat for Non‐Invasive Biomarker Monitoring: A Comprehensive Review

“…Moreover, the volume of sweat generated can range 15–100 µL, depending on the applied current density and IP time. [ 62 ] The schematic shown in Figure 3b describes a soft, adhesive tattoo like wearable patch for sweat alcohol sensing using IP. [ 11 ] The path consisted of two silver electrodes for applying IP and an enzymatic (alcohol oxidase (AOx)) electrochemical sensor (with a catalytic Prussian blue (PB) layer) attached near one of the electrode terminal, which could measure alcohol levels up to 40 m m in vitro.…”

A Comprehensive Review of the Recent Developments in Wearable Sweat-Sensing Devices

“…Adopting pharmacologic agents of sweat-stimulation such as hydrogel and pilocarpine can induce the skin to generate local sweat without requiring physical activity. The iontophoresis of pilocarpine can produce a sufficiently small amount of perspiration within the range of 15–100 μL [ 185 ]. Typically, the minimum volume capacity that a chemical sensor can react to and measure is at least 10 to 100 microliters [ 186 ].…”