Micropore visualization and lifetime following microneedle application to skin of differing pigments

微针应用于不同色素皮肤后微孔的可视化和寿命

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Abstract

Solid microneedles allow dermal delivery of drugs that cannot otherwise absorb through skin, via creation of epidermal micropores. The time that the micropores remain open (micropore lifetime) directly impacts drug delivery windows, and darker skin types have extended micropore lifetimes. Here we visualized dermal micropores and measured micropore lifetime in subjects with differing skin pigmentation (ClinicalTrials.gov identifier NCT04867733, registered 29th April 2021). Forty-nine subjects completed the study, self-identifying as Asian, Black, Caucasian, Latinx, and Bi-/multi-racial. Using a colorimeter, skin color was objectively measured and subjects were grouped according to dark (n = 13), medium (n = 19), or light (n = 17) skin. Stainless steel microneedles, 800 μm length, were applied to the arm. Impedance measurements confirmed a breach of skin barrier, suggesting adequate micropore formation. Micropore depth immediately post-microneedle application ranged from 70.3 to 106.6 μm across all subjects (n = 98 total measurements), but was not different between skin color groups, P > 0.05. OCT images were used to calculate micropore closure over 48 h. At 24 h there was no difference in % change in micropore depth between groups. By 48 h there was an 18.1% difference in micropore closure between the lightest and darkest skinned groups, P < 0.05. These data were in agreement with impedance-predicted micropore lifetimes. The longer micropore lifetime in darker skin was independent of micropore depth, and future mechanistic studies of physiological processes underlying these observations would contribute to an understudied area in skin of color research. Proof of concept pharmacokinetics studies would also be useful to investigate the full impact of these differences.

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