# Mechanisms of micropore closure after microneedle application in diverse skin types

> **NIH NIH F31** · UNIVERSITY OF IOWA · 2024 · $33,898

## Abstract

PROJECT ABSTRACT
Microneedles (MNs) are micron scale projections that allow for improved drug delivery through the skin via
formation of transient micropores. For successful transdermal drug delivery, it is crucial that the micropores
remain open (drug delivery ceases rapidly after micropore closure, usually within ~48 hrs). Delaying micropore
closure would be advantageous by allowing a longer period of drug delivery from each MN treatment. Previous
methods that have been explored for delaying micropore closure timeframes did not account for the
biochemical differences seen in diverse skin types; further, previous studies did not address the physiological
processes that impact micropore closure. We have shown that darker skin types have longer micropore
closure timeframes. This could result in altered therapeutic outcomes from unexpected drug delivery windows
in diverse skin types, which may be especially problematic for drugs with narrow therapeutic windows.
Catecholamines such as dopamine play a role in cutaneous wound healing and may mediate micropore
closure, but the direct role of dopamine in micropore closure has never been studied. Dopamine may alter
wound healing through dopamine receptor binding and subsequent cAMP modulation. Interestingly, melanin
production (responsible for skin color) also relies on the same dopaminergic precursors and alters intracellular
cAMP production. Therefore, we hypothesize that drug delivery through micropores in diverse skin types will
differ in a manner dependent upon micropore closure times, and variability in micropore closure among skin
types is influenced by dopamine secretion and receptor signaling. To test this, we will establish a translational
approach through two Aims. In Aim 1 we will assess the impact of differences in micropore closure times on
model drug absorption using a pharmacokinetic study. In Aim 2 we will investigate how dopamine D1/D2
receptor signaling alters microwound recovery using a dual in-vitro knockdown approach. The overall goal is to
identify a possible pharmaceutical target for delaying micropore closure, ultimately improving MN-assisted
transdermal drug delivery and informing development of better MN products for diverse populations.

## Key facts

- **NIH application ID:** 10827870
- **Project number:** 5F31AR081680-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Valeria Cota
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $33,898
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827870

## Citation

> US National Institutes of Health, RePORTER application 10827870, Mechanisms of micropore closure after microneedle application in diverse skin types (5F31AR081680-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10827870. Licensed CC0.

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