title: Micropore closure kinetics are delayed following microneedle insertion in elderly subjects.
abstract: Transdermal delivery is an advantageous method of drug administration, particularly for an elderly population. Microneedles (MNs) allow transdermal delivery of otherwise skin-impermeable drugs by creating transient micropores that bypass the barrier function of the skin. The response of aging skin to MNs has not been explored, and we report for the first time that micropore closure is delayed in elderly subjects in a manner that is dependent upon MN length, number, and occlusion of the micropores. Twelve control subjects (25.6±2.8years) and 16 elderly subjects (77.3±6.8years) completed the study. Subjects were treated with MNs of 500μm or 750μm length, in arrays containing 10 or 50 MNs. Impedance measurements made at baseline, post-MN insertion, and at predetermined time points demonstrated that restoration of the skin barrier is significantly slower in elderly subjects under both occluded and non-occluded conditions. This was confirmed via calculation of the total permeable area created by the micropores (which would approximate the area available for drug delivery), as well as calculation of the micropore half-life. This pilot study demonstrates that longer timeframes are required to restore the barrier function of aged skin following MN insertion, suggesting that drug delivery windows could be longer following one treatment with a MN array.
authors.affiliation: University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 115 S. Grand Ave, Iowa City, IA 52242, USA. Electronic address: megan-kelchen@uiowa.edu.
authors.forename: Megan N
authors.initials: MN
authors.lastname: Kelchen
authors.affiliation: University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 115 S. Grand Ave, Iowa City, IA 52242, USA. Electronic address: kyle-siefers@uiowa.edu.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Siefers
authors.affiliation: University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 115 S. Grand Ave, Iowa City, IA 52242, USA. Electronic address: courtney-converse@uiowa.edu.
authors.forename: Courtney C
authors.initials: CC
authors.lastname: Converse
authors.affiliation: University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 115 S. Grand Ave, Iowa City, IA 52242, USA. Electronic address: matthew.farley@unitypoint.org.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farley
authors.affiliation: University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 115 S. Grand Ave, Iowa City, IA 52242, USA. Electronic address: gholdren@gmail.com.
authors.forename: Grant O
authors.initials: GO
authors.lastname: Holdren
authors.affiliation: University of Iowa College of Pharmacy, Department of Pharmaceutical Sciences and Experimental Therapeutics, 115 S. Grand Ave, Iowa City, IA 52242, USA; University of Iowa Carver College of Medicine, Department of Dermatology, 200 Hawkins Dr, Iowa City, IA 52242, USA. Electronic address: nicole-brogden@uiowa.edu.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Brogden
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D016503:Drug Delivery Systems; D017097:Electric Impedance; D005260:Female; D006801:Humans; D008297:Male; D008845:Microinjections; D009339:Needles; D016062:Porosity; D012867:Skin / Q000033:anatomy & histology*; D055815:Young Adult
keywords: Drug delivery; Elderly; Impedance; Microneedle; Micropore; Transdermal