A Mouse Model for Tuberculosis Combined With Inhalable Imiquimod-PLGA Nanocomposite Particles Based on Macrophage Phenotype

In Vivo. 2022 Sep-Oct;36(5):2166-2172. doi: 10.21873/invivo.12942.

Abstract

Background/aim: In vivo models of tuberculosis are effective tools for developing new drugs. The objective of this study was to prepare in vivo models for tuberculosis by utilizing nanocomposite particles (NCPs) containing imiquimod-loaded poly(lactic-co-glycolic acid) nanoparticles.

Materials and methods: NCPs were prepared from dichloromethane with imiquimod and poly(lactic-co-glycolic acid) using a spray dryer. Mice were treated with NCPs in the lungs by inhalation, and then infection with Mycobacterium bovis bacille Calmette-Guerin was performed (treatment groups). The concentrations of the pro-inflammatory cytokines, tumor necrosis factor-α and interferon-γ were measured in bronchoalveolar lavage fluid using an enzyme-linked immunosorbent assay.

Results: When animals were treated with NCPs, the concentrations of tumor necrosis factor-α and interferon-γ in bronchoalveolar lavage fluid were significantly higher than in animals not treated with NCPs. In addition, high bacterial counts and circular granuloma were observed.

Conclusion: NCPs prepared in this study enhanced the level of inflammation in the lungs and support the preparation of in vivo models of tuberculosis.

Keywords: Nanocomposite particles; PLGA; in vivo model; inhalation; tuberculosis.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Imiquimod
  • Interferon-gamma
  • Lactic Acid
  • Macrophages
  • Mice
  • Nanocomposites*
  • Particle Size
  • Phenotype
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tuberculosis* / drug therapy
  • Tumor Necrosis Factor-alpha

Substances

  • Tumor Necrosis Factor-alpha
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Interferon-gamma
  • Imiquimod