Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, Iowa, USA.
Department of Dermatology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Skin Pharmacol Physiol. 2021;34(4):214-228. doi: 10.1159/000515454. Epub 2021 Apr 28.
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.
This pilot study explored if differences exist in micropore closure timeframes at 3 anatomical sites - upper arm, volar forearm, and abdomen.
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.
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.
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.
微孔的持续开放对于成功的微针（MN）药物输送策略至关重要。然而，微孔的寿命取决于内在的皮肤功能和解剖学特征，这些特征在不同的解剖部位有很大的差异。
本初步研究探讨了在三个解剖部位（上臂、掌侧前臂和腹部）的微孔闭合时间是否存在差异。
自我认定为亚洲人（n=9）、双/多种族（n=2）、黑人（n=9）、拉丁裔（n=6）和白人（n=9）的健康受试者（n=35）完成了这项研究。在上臂、掌侧前臂和腹部用 MN 处理；在 MN 前后测量皮肤阻抗和经皮水分丢失（TEWL）以确认微孔形成。通过测量阻抗 3 天来评估微孔寿命。使用三刺激比色计测量 L*值，该值量化皮肤的亮度/暗度。通过比较 MN 前后的阻抗测量来确定微孔寿命，并用数学建模预测微孔闭合半衰期。
MN 后 TEWL 的增加和阻抗的降低均具有统计学意义（p<0.05），证实了所有解剖部位的微孔成功形成。当根据受试者自我认定的种族/族裔群体分析数据时，腹部的平均微孔闭合时间（63.09±13.13h）长于上臂（60.34±14.69h）和掌侧前臂（58.29±16.76h）。解剖部位的预测微孔闭合半衰期为腹部（25.86±14.96h）≈上臂（23.69±13.67h）>掌侧前臂（20.2±11.99h）。组间差异无统计学意义。L*的客观分类表明，较深的肤色可能与腹部微孔闭合时间较长有关。
我们的结果表明，应用解剖部位可能不是微孔闭合时间存在显著变异性的来源。这些发现可能有助于减少在开发药物产品时需要明确考虑的生理参数数量，以支持 MN 辅助药物输送策略。
