Mannan-modified solid lipid nanoparticles for targeted gene delivery to alveolar macrophages

Pharm Res. 2010 Aug;27(8):1584-96. doi: 10.1007/s11095-010-0149-z. Epub 2010 Apr 27.

Abstract

Purpose: Cationic solid lipid nanoparticles (SLN) have established themselves during the past decades. They can efficiently bind DNA directly via ionic interaction and mediate gene transfection. One major problem with SLN is the lack of cell-targeting ability. In the present study, a mannan-based PE-grafted ligand was synthesized and used for the surface modification of DNA-loaded cationic SLN to prepare Man-SLN-DNA.

Methods: For in vitro test, the cytotoxicity and transfection investigation was carried out on murine macrophage cell line RAW 264.7. For in vivo evaluation, Man-SLN-DNA was delivered into the lung of the rats, and the alveolar macrophages (AM) were isolated for the fluorescence determination of transfection efficiency.

Results: When compared with non-modified SLN-DNA and Lipofectamine 2000-DNA, Man-SLN-DNA produced the highest gene expressions, especially in vivo.

Conclusion: These results demonstrated the active targeting ability of this kind of mannan-modified DNA-loaded vehicles, which may have great potential for targeted gene delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival
  • Concanavalin A / administration & dosage
  • Drug Delivery Systems
  • Genetic Therapy / methods*
  • Ligands
  • Lipids* / administration & dosage
  • Macrophages, Alveolar / metabolism*
  • Male
  • Mannans* / administration & dosage
  • Mannans* / chemistry
  • Mice
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / chemistry
  • Phosphatidylethanolamines / administration & dosage
  • Rats
  • Rats, Wistar

Substances

  • Ligands
  • Lipids
  • Lipofectamine
  • Mannans
  • Phosphatidylethanolamines
  • Concanavalin A