Drug packaging and delivery using perfluorocarbon nanoparticles for targeted inhibition of vascular smooth muscle cells

Acta Pharmacol Sin. 2009 Nov;30(11):1577-84. doi: 10.1038/aps.2009.146.

Abstract

Aim: To investigate the in vitro release profile of drugs encapsulated within perfluorocarbon (PFC) nanoparticles (NPs) and their ability to inhibit the activity of vascular smooth muscle cells (SMCs).

Methods: Dexamethasone phosphate (DxP) or dexamethasone acetate (DxA) was encapsulated into PFC nanoparticles using a high-pressure homogenous method. The morphology and size of the NPs were examined using scanning electron microscopy (SEM) and a laser particle size analyzer. Drug loading and in vitro release were assessed by high-performance liquid chromatography (HPLC). The impact of NP capsules on SMC proliferation, migration and apoptosis in vitro was assessed using cell counting kit-8, transwell cell migration and flow cytometry assays.

Results: The sizes of DxP-NPs and DxA-NPs were 224+/-6 nm and 236+/-9 nm, respectively. The encapsulation efficiency (EE) of DxP-NPs was 66.4%+/-1.0%, with an initial release rate of 77.2%, whereas the EE of DxA-NPs was 95.3%+/-1.3%, with an initial release rate of 23.6%. Both of the NP-coated drugs could be released over 7 d. Human umbilical artery SMCs were harvested and cultured for four to six passages. Compared to free DxP, SMCs treated with tissue factor (TF)-directed DxP-NPs showed significant differences in the inhibition of proliferation, migration and apoptosis (P<0.05).

Conclusion: The results collectively suggest that PFC nanoparticles will be beneficial for targeted drug delivery because of the sustained drug release and effective inhibition of SMC proliferation and migration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Delayed-Action Preparations
  • Dexamethasone / administration & dosage
  • Dexamethasone / analogs & derivatives*
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Fluorocarbons / chemistry*
  • Humans
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Nanoparticles*
  • Particle Size
  • Umbilical Arteries / cytology
  • Umbilical Arteries / metabolism

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Fluorocarbons
  • dexamethasone 21-phosphate
  • Dexamethasone
  • dexamethasone acetate