Passive diffusion of pilocarpine following microneedle pretreatment is ineffective for palmar sweat induction

Palmar sweating plays a key role in enhancing hand grip function and is implicated in clinical conditions such as hyperhidrosis and anhidrosis. However, our understanding of the mechanisms underlying palmar sweating remains unresolved. This is in part because pharmacological investigation of palmar sweat gland function is limited by the thick stratum corneum, which restricts transdermal drug delivery. We therefore assessed whether passive diffusion of pilocarpine induced by pretreatment of palmar skin with microneedles can induce sweating. In 30 healthy adults (15 males), sweat induction was compared among three delivery methods of pilocarpine by iontophoretic administration with and without microneedle pretreatment and passive diffusion after microneedle pretreatment. Local palmar sweat rate was measured using the ventilated capsule technique, and pilocarpine delivery was quantified by high-performance liquid chromatography. Passive diffusion following microneedle pretreatment induced a lower sweat rate than iontophoresis with and without microneedle pretreatment (0.21 ± 0.07 vs. 0.61 ± 0.28 and 0.47 ± 0.27 mg·cm⁻²·min⁻¹, P < 0.001). Passive diffusion-induced sweating did not correlate with iontophoresis after microneedles (r = 0.346, P < 0.065). While microneedle pretreatment enhanced pilocarpine delivery (0.54 ± 0.09 mg, P ≤ 0.002), responses did not differ between iontophoresis alone and passive diffusion (0.48 ± 0.06 and 0.49 ± 0.06 mg, P = 0.876). Altogether, while we showed that passive diffusion of pilocarpine following microneedle pretreatment induced palmar sweating, the magnitude of this response was not comparable to the levels with iontophoresis, probably due to thick stratum corneum and transient skin barrier disruption.