Exploring Extracellular Vesicles Nanocapsules in Hydrogel Delivery for Canine Atopic Dermatitis: An Anti-Inflammatory Approach

Juliana da Matta Furniel Dutra; Fabio Moyses Lins Dantas; Caroline Pinho Winck; Anael Viana Pinto Alberto; Debora Vieira Way; Adriana Cristina Motta; Elba dos Santos de Oliveira; Maria Lucila d’Ottaviano Nápole; Juliano C da Silveira; Edson Guimarães Lo Turco

doi:10.21467/anr.8.1.1-17

Authors

Juliana da Matta Furniel Dutra Medmep - Molecular Biology Division https://orcid.org/0009-0003-0416-044X
Fabio Moyses Lins Dantas Division of Materials, Instituto Nacional de Tecnologia - INT https://orcid.org/0000-0002-2233-818X
Caroline Pinho Winck Medmep https://orcid.org/0000-0002-9995-3105
Anael Viana Pinto Alberto Division of Materials, Instituto Nacional de Tecnologia - INT https://orcid.org/0000-0002-4970-6026
Debora Vieira Way Division of Materials, Instituto Nacional de Tecnologia - INT https://orcid.org/0000-0003-1248-2361
Adriana Cristina Motta Division of Materials, Instituto Nacional de Tecnologia - INT https://orcid.org/0000-0002-6762-0234
Elba dos Santos de Oliveira Division of Materials, Instituto Nacional de Tecnologia - INT https://orcid.org/0009-0008-6542-8696
Maria Lucila d’Ottaviano Nápole Medmep https://orcid.org/0009-0005-2784-6369
Juliano C da Silveira Universidade de São Paulo https://orcid.org/0000-0002-4796-6393
Edson Guimarães Lo Turco Universidade Federal de São Paulo- Departamento de Cirurgia - Disciplina de Urologia https://orcid.org/0000-0002-3509-847X

DOI:

https://doi.org/10.21467/anr.8.1.1-17

Abstract

This study aims to evaluate the anti-inflammatory potential of nanoencapsulated extracellular vesicles (EV) derived from canine mesenchymal stem cells (MSCs) in treating atopic dermatitis. It seeks to determine the efficacy of these EV in modulating cytokine responses, specifically targeting IL-2, IL-4, IL-5, IL-6, IL-10, IL13, and IL-31, which are crucial in the pathophysiology of cutaneous inflammatory disorders. Materials and Methods: MSCs were cultured from adipose tissue and induced to produce EVs. They were then isolated through ultracentrifugation, characterized for particle size and morphology, and encapsulated within calcium alginate nanogels. The anti-inflammatory activity was assessed in vitro using human keratinocyte cultures primed with IFN-gamma and treated with both free and nanoencapsulated EV. The expression of inflammatory cytokines was analyzed through RTq-PCR and protein ELISA Multiplex (Luminex®). Results: The study found that both free and nanoencapsulated EV significantly reduced the expression of IL-2, IL-4, IL-5, IL6, IL-10, IL-13, and IL-31 in IFN-gamma primed keratinocytes. Nanoencapsulation with alginate notably enhanced the delivery efficiency, targeted release, and stability of the EV, leading to a more pronounced reduction in cytokine expression compared to free EV. Conclusion: Nanoencapsulated EV derived from canine MSCs demonstrate significant anti-inflammatory potential, offering a promising therapeutic strategy for atopic dermatitis and other inflammatory conditions. This approach not only preserves the bioactivity of EV but also improves their therapeutic applicability through enhanced delivery and stability. The findings underscore the potential of nanoencapsulation technology in advancing novel therapeutic strategies across human and veterinary medicine, highlighting the importance of cross-disciplinary research in developing effective healthcare solutions.

Keywords:

mesenchymal stem cells, extracellular vesicles, canine atopic dermatitis

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