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Local sustained delivery of anti-IL-17A antibodies limits inflammatory bone loss in murine experimental periodontitis
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Accession number :
- edsair.doi.dedup.....104f183461c8e2d0d66ae89e3c168728