Anti-inflammatory effect of IL-1ra-loaded dextran/PLGA microspheres on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages in vitro and in vivo in a rat model of periodontitis

Biomed Pharmacother. 2021 Feb:134:111171. doi: 10.1016/j.biopha.2020.111171. Epub 2020 Dec 28.

Abstract

Periodontitis is a multifactorial chronic infectious disease leading to a host immune response involving inflammatory cytokines, especially IL-1β, which is the main reason for further developing this disease. IL-1 receptor antagonist (IL-1ra) binds IL-1 receptor, inhibiting IL-1β 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.

Keywords: Inflammation; Interleukin 1 receptor antagonist protein; Interleukin-1; Microspheres; Periodontitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dextrans / chemistry*
  • Disease Models, Animal
  • Drug Carriers*
  • Drug Compounding
  • Interleukin 1 Receptor Antagonist Protein / chemistry
  • Interleukin 1 Receptor Antagonist Protein / pharmacology*
  • Lipopolysaccharides / isolation & purification
  • Lipopolysaccharides / toxicity
  • Macrophage Activation / drug effects*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • Microspheres
  • Periodontitis / immunology
  • Periodontitis / metabolism
  • Periodontitis / prevention & control*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Porphyromonas gingivalis / chemistry
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Dextrans
  • Drug Carriers
  • Interleukin 1 Receptor Antagonist Protein
  • Lipopolysaccharides
  • Polylactic Acid-Polyglycolic Acid Copolymer