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Keratinocyte Exosomes for Topical Delivery of Tofacitinib in Treatment of Psoriasis: An in Vitro/ in Vivo Study in Animal Model of Psoriasis Publisher Pubmed



Dehghani P1 ; Varshosaz J1 ; Mirian M2 ; Minaiyan M3 ; Kazemi M4, 5 ; Bodaghi M6
Authors
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Authors Affiliations
  1. 1. Novel Drug Delivery Systems Research Center, Department of Pharmaceutics, Faculty of Pharmacy, Isfahan University of Medical Sciences, PO Box 81745-359, Isfahan, Iran
  2. 2. Department of Pharmaceutical Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Genetics and Molecular biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Reproductive Sciences and Sexual Health Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Department of Engineering School of Science and Technology Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom

Source: Pharmaceutical Research Published:2024


Abstract

Introduction: Exosomes are extracellular vesicles in the range of 40-150 nm released from the cell membrane. Exosomes secreted by keratinocytes can communicate with other keratinocytes and immune cells with specific biomarkers at their surface, which may be effective on inflammation of psoriasis and its pathogenesis. 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. Graphical abstract: (Figure presented.) © The Author(s) 2024. corrected publication 2024.
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