Local sustained delivery of anti-IL-17A antibodies limits inflammatory bone loss in murine experimental periodontitis
| Autor: | Laura L. Thomas, Zhe Zhuang, Sarah L. Gaffen, Steven R. Little, Cinthia M F Pacheco, Mostafa S. Shehabeldin, Gustavo Pompermaier Garlet, Sayuri Yoshizawa, Konstantinos Verdelis, Charles Sfeir, Katia L M Maltos |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Drug Compounding medicine.medical_treatment Immunology Alveolar Bone Loss Capsules Inflammation Osteolysis Bone resorption Pathogenesis Mice 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Immune system Polylactic Acid-Polyglycolic Acid Copolymer medicine Animals Immunology and Allergy Periodontitis Dental alveolus REABSORÇÃO ÓSSEA ALVEOLAR Mice Inbred BALB C business.industry Interleukin-17 OSSO E OSSOS Periodontium medicine.disease Antibodies Neutralizing Disease Models Animal Drug Liberation Treatment Outcome Cytokine medicine.symptom business 030215 immunology |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Periodontal disease (PD) is a chronic destructive inflammatory disease of the tooth-supporting structures that leads to tooth loss at its advanced stages. Although the disease is initiated by a complex organization of oral microorganisms in the form of a plaque biofilm, it is the uncontrolled immune response to periodontal pathogens that fuels periodontal tissue destruction. IL-17A has been identified as a key cytokine in the pathogenesis of PD. Despite its well documented role in host defense against invading pathogens at oral barrier sites, IL-17A–mediated signaling can also lead to a detrimental inflammatory response, causing periodontal bone destruction. In this study, we developed a local sustained delivery system that restrains IL-17A hyperactivity in periodontal tissues by incorporating neutralizing anti–IL-17A Abs in poly(lactic-coglycolic) acid microparticles (MP). This formulation allowed for controlled release of anti–IL-17A in the periodontium of mice with ligature-induced PD. Local delivery of anti–IL-17A MP after murine PD induction inhibited alveolar bone loss and osteoclastic activity. The anti–IL-17A MP formulation also decreased expression of IL-6, an IL-17A target gene known to induce bone resorption in periodontal tissues. This study demonstrates proof of concept that local and sustained release of IL-17A Abs constitutes a promising therapeutic strategy for PD and may be applicable to other osteolytic bone diseases mediated by IL-17A–driven inflammation. |
| Databáze: | OpenAIRE |
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