Ultra-small solid archaeolipid nanoparticles for active targeting to macrophages of the inflamed mucosa

Nanomedicine (Lond). 2017 May;12(10):1165-1175. doi: 10.2217/nnm-2016-0437. Epub 2017 Apr 27.

Abstract

Aim: Develop nanoparticulate agents for oral targeted delivery of dexamethasone (Dex) to macrophages of inflamed mucosa.

Materials & methods: Solid archaeolipid nanoparticles (SAN-Dex) (compritol/Halorubrum tebenquichense polar archaeolipids/soybean phosphatidylcholine/Tween-80 4; 0.9; 0.3; 3% w/w) loaded with Dex were prepared. Their mucopenetration, stability under digestion and in vitro anti-inflammatory activity, were determined.

Results: Ultra-small SAN-Dex strongly reduced the levels of TNF-α, IL-6 and IL-12 on J774A1 cells stimulated with lipopolysaccharides as compared with free Dex or loaded in ordinary solid lipid nanoparticles-Dex. After in vitro digestion, the anti-inflammatory activity of SAN-Dex was retained, while that of solid lipid nanoparticles-Dex was lost.

Conclusion: Because of their structural and pharmacodynamic features, SAN-Dex may be suitable for oral targeted delivery to inflamed mucosa.

Keywords: digestion stability; inflammatory bowel disease; oral delivery.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Caco-2 Cells
  • Cell Line
  • Dexamethasone / administration & dosage*
  • Dexamethasone / pharmacology
  • Drug Delivery Systems
  • Halorubrum / chemistry
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Interleukin-12 / immunology
  • Interleukin-6 / immunology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Lipids / chemistry*
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Nanoparticles / chemistry*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • Interleukin-6
  • Lipids
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Dexamethasone