Dextran-based therapeutic nanoparticles for hepatic drug delivery

Nanomedicine (Lond). 2016 Oct;11(20):2663-2677. doi: 10.2217/nnm-2016-0156. Epub 2016 Sep 15.

Abstract

Aim: Evaluation of dextran-based nanoparticles (DNP) as a drug delivery system to target myeloid cells of the liver.

Materials & methods: DNP were synthesized and optionally PEGylated. Their toxicity and cellular uptake were studied in vitro. Empty and siRNA-carrying DNP were tested in vivo with regard to biodistribution and cellular uptake.

Results: In vitro, DNP were taken up by cells of the myeloid lineage without compromising their viability. In vivo, empty and siRNA-carrying DNP distributed to the liver where a single treatment addressed approximately 70% of macrophages and dendritic cells. Serum parameters indicated no in vivo toxicity.

Conclusion: DNP are multifunctional liver-specific drug carriers which lack toxic side effects and may be utilized in clinical applications targeting liver macrophages.

Keywords: PEGylation; biodegradable; dendritic cell; dextran; drug delivery; liver targeting; macrophage; nanoparticles; siRNA.

MeSH terms

  • 3T3 Cells
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Survival
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Dextrans / chemistry*
  • Drug Carriers / chemistry
  • Drug Carriers / toxicity
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Particle Size
  • Polyethylene Glycols / chemistry
  • RAW 264.7 Cells
  • RNA, Small Interfering / administration & dosage*
  • Surface Properties
  • Tissue Distribution

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 protein, mouse
  • Dextrans
  • Drug Carriers
  • RNA, Small Interfering
  • Polyethylene Glycols