Homogeneous nanoparticles to enhance the efficiency of a hydrophobic drug, antihyperlipidemic probucol, characterized by solid-state NMR

Mol Pharm. 2010 Feb 1;7(1):299-305. doi: 10.1021/mp900254y.

Abstract

A low absorption in the gastrointestinal tract of hydrophobic pharmaceutical compounds in use today considerably limits their bioavailability, and therefore they are taken in large doses in order to reach the therapeutic plasma concentration, which inevitably results in undesired side effects. In this study, we demonstrate a new nanoparticle approach to overcome this problem, and our experimental results show that this approach has a high efficiency of drug loading and is easily adaptable to industrial scale. Characterization of nanoparticles containing a cholesterol-lowering hydrophobic drug, probucol, using a variety of biophysical techniques revealed higher homogeneity of these particles compared to those prepared using other approaches. Intermolecular interactions of these nanoparticles are probed at high resolution by magic angle spinning solid-state NMR experiments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Membrane Permeability
  • Drug Delivery Systems
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Hypolipidemic Agents / administration & dosage*
  • Hypolipidemic Agents / pharmacokinetics
  • Magnetic Resonance Spectroscopy
  • Microscopy, Electron, Scanning
  • Models, Molecular
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Particle Size
  • Polymethacrylic Acids
  • Probucol / administration & dosage*
  • Probucol / pharmacokinetics
  • Sodium Dodecyl Sulfate

Substances

  • Hypolipidemic Agents
  • Polymethacrylic Acids
  • methylmethacrylate-methacrylic acid copolymer
  • Sodium Dodecyl Sulfate
  • Probucol