Microneedle and iontophoresis mediated delivery of methotrexate into and across healthy and psoriatic skin.

Diseased skin In vitro permeation testing Iontophoresis Microneedle Psoriasis Psoriatic skin Topical and Transdermal delivery

Journal

International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127

Informations de publication

Date de publication:
25 Apr 2022
Historique:
received: 10 12 2021
revised: 13 03 2022
accepted: 18 03 2022
pubmed: 26 3 2022
medline: 14 4 2022
entrez: 25 3 2022
Statut: ppublish

Résumé

Psoriasis is a condition of the skin which involves scales, dry patches, and inflammation. Methotrexate (logP: -1.8, MW:454.44 g/mol) is administered orally or intravenously to treat psoriasis. The first-pass metabolism and systemic toxicity can be avoided by administration via skin. Topical and transdermal delivery of methotrexate using iontophoresis and microneedles, alone and in combination was investigated using full-thickness healthy human skin. It is also equally relevant to evaluate the delivery into and across damaged/diseased skin. Hence, this study investigated the delivery of methotrexate using ex vivo healthy and psoriatic human skin to understand the effect of skin disease condition on delivery of methotrexate via skin. A lower resistance and a higher TEWL for psoriatic skin indicated damaged barrier function, while histology studies indicated epithelial hyperproliferation and elongated rete ridges. Using the optimized iontophoretic parameters, there was no significant difference in receptor delivery for psoriatic skin (39.51 ± 4.45 µg/sq.cm) as compared to healthy skin (43.15 ± 0.83 µg/sq.cm). However, methotrexate delivery into psoriatic skin (126.23 ± 24.65 µg/sq.cm) was significantly higher as compared to healthy skin (12.02 ± 4.89 µg/sq.cm). Thus, significantly higher total delivery was observed from psoriatic skin than healthy skin.

Identifiants

pubmed: 35331833
pii: S0378-5173(22)00248-4
doi: 10.1016/j.ijpharm.2022.121693
pmc: PMC9022631
mid: NIHMS1792297
pii:
doi:

Substances chimiques

Methotrexate YL5FZ2Y5U1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

121693

Subventions

Organisme : FDA HHS
ID : R44 FD005345
Pays : United States
Organisme : NIH HHS
ID : U42 OD011158
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier B.V. All rights reserved.

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Auteurs

Deepal Vora (D)

Center for Drug Delivery Research, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.

Harsha T Garimella (HT)

CFD Research Corporation, 701 McMillian Way, Huntsville, AL 35806, USA.

Carrie L German (CL)

CFD Research Corporation, 701 McMillian Way, Huntsville, AL 35806, USA.

Ajay K Banga (AK)

Center for Drug Delivery Research, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA. Electronic address: banga_ak@mercer.edu.

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Classifications MeSH