Mannose-functionalized solid lipid nanoparticles are effective in targeting alveolar macrophages

Eur J Pharm Sci. 2018 Mar 1:114:103-113. doi: 10.1016/j.ejps.2017.12.006. Epub 2017 Dec 8.

Abstract

Mannose receptor is highly expressed on alveolar macrophages, being a potential target to promote the specific local drug delivery of anti-tuberculosis agents through the use of functionalized nanocarriers. In this work, isoniazid (Isn)-loaded solid lipid nanoparticles (SLN), reinforced with stearylamine (SA) were produced by double emulsion technique and further surface-functionalized with mannose in a straightforward chemical approach. Upon pre-formulation assessment, SLN close to 500 nm average size, positively charged and with association efficiency of ISN close to 50% were obtained. Functionalization with mannose was performed after SLN production and confirmed by Fourier transform infrared spectroscopy (FTIR). Both functionalized and non-functionalized SLN demonstrated to devoid of toxicity when tested in human lung epithelial cell line (NCI-H441) and differentiated THP-1 (dTHP-1), reducing the intrinsic cytotoxicity of Isn when incorporated into SLN. Uptake studies were conducted on same macrophage-like cells and the results showed that fluorescent mannosylated SLN (M-SLN) were more efficient in be internalized comparatively to SLN. Moreover, the uptake of M-SLN was reduced when cells were pre-incubated with mannose, demonstrating the receptor-dependence internalization of functionalized SLN. These functionalized nanocarriers may represent a useful platform to target alveolar macrophages for delivering anti-infective drugs.

Keywords: Alveolar macrophage; Macrophage nanoparticle uptake; Mannose functionalization; Solid lipid nanoparticles.

MeSH terms

  • Drug Delivery Systems / methods
  • Excipients / administration & dosage
  • Excipients / chemical synthesis
  • Excipients / metabolism
  • Fatty Acids / administration & dosage*
  • Fatty Acids / chemical synthesis
  • Fatty Acids / metabolism
  • Humans
  • Lipids
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / metabolism
  • Mannose / administration & dosage*
  • Mannose / chemical synthesis
  • Mannose / metabolism
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism
  • Stearic Acids / administration & dosage*
  • Stearic Acids / chemical synthesis
  • Stearic Acids / metabolism
  • THP-1 Cells
  • Triglycerides / administration & dosage*
  • Triglycerides / chemical synthesis
  • Triglycerides / metabolism

Substances

  • Excipients
  • Fatty Acids
  • Lipids
  • Stearic Acids
  • Triglycerides
  • witepsol
  • glyceryl behenate
  • stearic acid
  • Mannose