Keratinocyte exosomes for topical delivery of tofacitinib in treatment of psoriasis: an in vitro/ in vivo study in animal model of psoriasis

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Dehghani, P, Varshosaz, J, Mirian, M, Minaiyan, M, Kazemi, M and Bodaghi, M ORCID: https://orcid.org/0000-0002-0707-944X, 2024. Keratinocyte exosomes for topical delivery of tofacitinib in treatment of psoriasis: an in vitro/ in vivo study in animal model of psoriasis. Pharmaceutical Research. ISSN 0724-8741

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Official URL: https://doi.org/10.1007/s11095-023-03648-0

Abstract

Objective: The present study aimed to formulate and study effectiveness of an exosomal delivery system of tofacitinib (TFC).

Methods: TFC was loaded by different methods in exosomes and then characterized for particle size, zeta potential, drug loading efficiency, and release efficiency. By comparing these parameters, the probe sonication method was chosen to load TFC into exosomes. The MTT assay was used to compare the cytotoxicity of the free drug with the TFC-loaded exosomes (TFC-Exo), and Real-time PCR was used to determine the expression levels of several genes involved in psoriasis expressed in the A-431 keratinocyte and their suppression after treatment. Animal model of psoriasis was induced in BALB/c mice by imiquimod and the efficacy of free TFC, and TFC-Exo were studies on macroscopic appearance and histopathological symptoms.

Results: Exosomes encapsulating TFC showed lower cytotoxicity in MTT assay, higher suppression the expression of TNF-a, IL-23, IL-6, and IL-15 genes in real-time PCR and better therapeutic effect on animal models compered to free TFC.

Conclusions: This method of drug delivery for TFC may be effective on enhancing its therapeutic effects and reduction its side effects favorably in chronic administration.

Item Type:	Journal article
Publication Title:	Pharmaceutical Research
Creators:	Dehghani, P., Varshosaz, J., Mirian, M., Minaiyan, M., Kazemi, M. and Bodaghi, M.
Publisher:	Springer Science and Business Media LLC
Date:	23 January 2024
ISSN:	0724-8741
Identifiers:	Number Type 10.1007/s11095-023-03648-0 DOI 1855513 Other
Rights:	© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	29 Jan 2024 09:23
Last Modified:	29 Jan 2024 09:23
URI:	https://irep.ntu.ac.uk/id/eprint/50753