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

Author(s):Show less -

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.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 19, p. 18-pg., 2024-01-01.

Abstract

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)

• FAPESP's process: 18/26383-7 - Effects of lipidic nucleus nanocapsule containing Annexin A1 in Ulcerative Colitis model induced in mice
• Grantee: Milena Fronza Broering
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/12301-1 - Synthesis of ordered mesoporous silica with different structures and morphologies
• Grantee: Pedro Leonidas Oseliero Filho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/07007-7 - Multi-User Equipment approved in grant 17/17844-8: SAXS detector system upgrade with sample holder and window
• Grantee: Marcia Carvalho de Abreu Fantini
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 17/17844-8 - Nanostructured silica as a protective vehicle for vaccines and biomolecules
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/11602-0 - Annexin A1 and neutrophils: mechanisms involved in gestation, Melanoma metastasis and Intestinal Ulcerative Disease
• Grantee: Sandra Helena Poliselli Farsky
• Support Opportunities: Regular Research Grants