Prolonged and localized sweat stimulation by iontophoretic delivery of the slowly-metabolized cholinergic agent carbachol

Abstract

Background: Continuous non-invasive sampling and sensing of multiple classes of analytes could revolutionize medical diagnostics and wearable technologies, but also remains highly elusive because of the many confounding factors for candidate biofluids such as interstitial fluid, tears, saliva, and sweat. Eccrine sweat biosensing has seen a recent surge in demonstrations of wearable sampling and sensing devices. However, for subjects at rest, access to eccrine sweat is highly limited and unpredictable compared to saliva and tears.

Objective: Reported here is a prolonged and localized sweat stimulation by iontophoretic delivery of the slowly-metabolized nicotinic cholinergic agonist carbachol.

Methods: Presented here are detailed measurements of natural baseline sweat rates across multiple days, confirming a clear need for localized sweat stimulation. Iontophoresis was performed with either carbachol or pilocarpine in order to stimulate sweat in subjects at rest. Furthermore, improved methods of quantifying sweat generation rates (nL/min/gland) are demonstrated.

Results: In-vivo testing reveals that carbachol stimulation can surpass a major goal of 24-h sweat access, in some cases providing more than an order of magnitude longer duration than stimulation with commonly-used pilocarpine. Also demonstrated is reduction of the traditional iontophoretic dosage for sweat stimulation (<5.25-42mC/cm²). This increases the viability of repeated dosing as demonstrated herein, and for carbachol is as much as 100-1000X less than used for other applications.

Conclusion: This work is not only significant for wearable sweat biosensing technology, but could also have broader impact for those studying topical skin products, antiperspirants, textiles and medical adhesives, nerve disorders, the effects of perspiration on skin-health, skin related diseases such as idiopathic pure sudomotor failure and hyperhidrosis, and other skin- and perspiration-related applications.

Keywords: Carbachol; Eccrine sweat gland; Iontophoresis; Pilocarpine; Sweat stimulation.