RESUMO
Periodontitis is a multifactorial chronic infectious disease leading to a host immune response involving inflammatory cytokines, especially IL-1ß, which is the main reason for further developing this disease. IL-1 receptor antagonist (IL-1ra) binds IL-1 receptor, inhibiting IL-1ß signaling and reducing the levels of other cytokines closely related to periodontitis, such as IL-6 and TNF-α. Therefore, the use of IL-1ra to inhibit periodontitis development in a system, ensuring its sustained release, might be an effective way to combat this disease. Hence, in this study, a novel IL-1ra-loaded dextran/PLGA microsphere was developed to allow the sustained release of IL-1ra and enhance the anti-inflammatory properties. Therefore, this study's purposes were to develop a novel periodontal treatment for inhibition and treatment of periodontitis and evaluate the sustained-release effect and anti-inflammatory properties of IL-1ra-loaded dextran/PLGA microspheres in vitro by cell experiments and in vivo by animal experiments. The results showed that IL-1ra-loaded dextran/PLGA microspheres were non-toxic both in vitro and in vivo and could be used as a safe and effective treatment. In addition, these microspheres could significantly prolong the half-life of IL-1ra drug, exerting a useful anti-inflammatory effect in macrophages stimulated with P. gingivalis lipopolysaccharide and in rats with periodontitis. In conclusion, IL-1ra-loaded dextran/PLGA microsphere might be a useful tool to combat periodontal disease.
Assuntos
Anti-Inflamatórios/farmacologia , Dextranos/química , Portadores de Fármacos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Periodontite/prevenção & controle , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Anti-Inflamatórios/química , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/química , Lipopolissacarídeos/isolamento & purificação , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Microesferas , Periodontite/imunologia , Periodontite/metabolismo , Porphyromonas gingivalis/química , Células RAW 264.7 , Ratos Sprague-DawleyRESUMO
Periodontitis is a chronic infectious disease, the course and progression of which are determined by the interaction between microorganisms and the host. Interleukin 1ß plays an important role in the destruction of periodontal tissues. Interleukin 1 receptor antagonist (IL-1ra) can inhibit the biological activity of IL-1ß without triggering any intracellular signaling. This study aimed to prepare IL-1ra-loaded dextran/PLGA microspheres and evaluate the physical and chemical characteristics and anti-inflammatory properties. Results suggested that the microspheres can be easily prepared into a drug carrier with good biocompatibility and can effectively inhibit the gene expression of pro-inflammatory factors induced by IL-1ß in human gingival fibroblasts. Hence, the microspheres are excellent candidate for periodontitis treatment.
