Micropore Closure Rates following Microneedle Application at Various Anatomical Sites in Healthy Human Subjects

Abstract

Introduction: The continuous availability of open micropores is crucial for a successful microneedle (MN) drug delivery strategy. However, micropore lifetime depends on intrinsic skin functional and anatomical characteristics, which vary significantly at different anatomical sites. Objective: This pilot study explored if differences exist in micropore closure timeframes at 3 anatomical sites - upper arm, volar forearm, and abdomen. Methods: Healthy subjects (n = 35) self-identifying as Asian (n = 9), Bi-/multiracial (n = 2), Black (n = 9), Latino (n = 6), and White (n = 9) completed the study. The upper arm, volar forearm, and abdomen were treated with MNs; skin impedance and transepidermal water loss (TEWL) were measured at baseline and post-MN to confirm micropore formation. Impedance was measured for 3 days to evaluate micropore lifetime. Measurements of L∗, which quantifies the skin lightness/darkness, were made using a tristimulus colorimeter. Micropore lifetime was determined by comparing baseline and post-MN impedance measurements, and micropore closure half-life was predicted using mathematical modeling. Results: Post-MN increase in TEWL and decrease in impedance were significant (p < 0.05), confirming successful micropore formation at all anatomical sites. When data were analyzed according to subject self-identified racial/ethnic groups, the mean micropore closure time at the abdomen (63.09 ± 13.13 h) was longer than the upper arm (60.34 ± 14.69 h) and volar forearm (58.29 ± 16.76 h). The predicted micropore closure half-life at anatomical sites was the abdomen (25.86 ± 14.96 h) ≈ upper arm (23.69 ± 13.67 h) > volar forearm (20.2 ± 11.99 h). Differences were not statistically significant between groups. Objective categorization by L∗ showed that the darker skin may be associated with longer micropore closure time at the abdomen site. Conclusions: Our results suggest that anatomical site of application may not be a source of significant variability in micropore closure time. These findings may help reduce the number of physiological parameters that need to be explicitly considered when developing drug products to support MN-assisted drug delivery strategies.