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Mechanisms of micropore closure after microneedle application in diverse skin types

Award Number: F31AR081680
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Mechanisms of micropore closure after microneedle application in diverse skin types - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $33,538 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	9/9/2025	NON-COMPETING CONTINUATION	$33,538
														Subtotal = $33,538

Issue Date FY: 2024 ( Subtotal = $33,898 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	6/6/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/20/2024	NON-COMPETING CONTINUATION	$32,618
														Subtotal = $33,898

Issue Date FY: 2023 ( Subtotal = $32,591 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/24/2023	NEW	$32,591
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	2/24/2023	NEW	$0
														Subtotal = $32,591

Grand Total All Awards = $100,027

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Mechanisms of micropore closure after microneedle application in diverse skin types

Award Number: F31AR081680

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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