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Development of Ac2-26 Mesoporous Microparticle System as a Potential Therapeutic Agent for Inflammatory Bowel Diseases

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Broering, Milena Fronza ; Oseliero Filho, Pedro Leonidas ; Borges, Pamela Pacassa ; da Silva, Luis Carlos Cides ; Knirsch, Marcos Camargo ; Xavier, Luana Filippi ; Scharf, Pablo ; Sandri, Silvana ; Stephano, Marco Antonio ; de Oliveira, Fernando Anselmo ; Sayed, Ibrahim M. ; Gamarra, Lionel Fernel ; Das, Soumita ; Fantini, Marcia C. A. ; Farsky, Sandra H. P.
Número total de Autores: 15
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 19, p. 18-pg., 2024-01-01.
Resumo

Introduction: Inflammatory bowel diseases (IBDs) disrupt the intestinal epithelium, leading to severe chronic inflammation. Current therapies cause adverse effects and are expensive, invasive, and ineffective for most patients. Annexin A1 (AnxA1) is a pivotal endogenous anti-inflammatory and tissue repair protein in IBD. Nanostructured compounds loading AnxA1 or its active N -terminal mimetic peptides improve IBD symptomatology. Methods: To further explore their potential as a therapeutic candidate, the AnxA1 N -terminal mimetic peptide Ac2-26 was incorporated into SBA-15 ordered mesoporous silica and covered with EL30D-55 to deliver it by oral treatment into the inflamed gut. Results: The systems SBA-Ac2-26 developed measurements revealed self-assembled rod-shaped particles, likely on the external surface of SBA-15, and 88% of peptide incorporation. SBA-15 carried the peptide Ac2-26 into cultured Raw 264.7 macrophages and Caco-2 epithelial cells. Moreover, oral administration of Eudragit-SBA-15-Ac2-26 (200 mu g; once a day; for 4 days) reduced colitis clinical symptoms, inflammation, and improved epithelium recovery in mice under dextran-sodium sulfate-induced colitis. Discussion: The absorption of SBA-15 in gut epithelial cells is typically low; however, the permeable inflamed barrier can enable microparticles to cross, being phagocyted by macrophages. These findings suggest that Ac2-26 is successfully delivered and binds to its receptors in both epithelial and immune cells, aligning with the clinical results. Conclusion: Our findings demonstrate a simple and cost-effective approach to delivering Ac2-26 orally into the inflamed gut, highlighting its potential as non -invasive IBD therapy. (AU)

Processo FAPESP: 18/26383-7 - Efeitos da nanocápsula de núcleo lipídico contendo Anexina A1 em modelo de Colite Ulcerativa induzida em camundongos
Beneficiário:Milena Fronza Broering
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 19/12301-1 - Síntese de sílicas mesoporosas ordenadas com diferentes estruturas e morfologias
Beneficiário:Pedro Leonidas Oseliero Filho
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 19/07007-7 - EMU concedido no processo 17/17844-8:Upgrade de sistema de detecção para SAXS com porta amostra e janela
Beneficiário:Marcia Carvalho de Abreu Fantini
Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
Processo FAPESP: 17/17844-8 - Sílica nanoestruturada como veículo protetor de vacinas e biomoléculas
Beneficiário:Osvaldo Augusto Brazil Esteves Sant'Anna
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 22/11602-0 - Anexina A1 e neutrófilos: mecanismos envolvidos na gestação, na metástase do Melanoma e na Doença Ulcerativa Intestinal
Beneficiário:Sandra Helena Poliselli Farsky
Modalidade de apoio: Auxílio à Pesquisa - Regular