All-trans-retinoic acid nanodisks

Int J Pharm. 2007 Jul 18;339(1-2):246-50. doi: 10.1016/j.ijpharm.2007.02.033. Epub 2007 Mar 6.

Abstract

Nanodisks are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by association of apolipoprotein molecules. Self-assembled ND particles enriched with all-trans-retinoic acid (ATRA) (phospholipid:ATRA molar ratio = 5.5:1) were generated wherein all reaction components were solubilized. ATRA-ND migrated as a single band (Stokes' diameter approximately 20 nm) on native gradient polyacrylamide gel electrophoresis. ATRA, phospholipid and apolipoprotein co-eluted from a Sepharose 6B gel filtration column, consistent with stable integration of ATRA into the ND particle milieu. Spectroscopic analysis of ATRA-ND in buffer yielded an absorbance spectrum characteristic of ATRA. ATRA-ND mediated time-dependent inhibition of cultured HepG2 cell growth more effectively than free ATRA. The nanoscale size of the formulation particles and the stable integration of biologically active ATRA suggest ND represent a potentially useful vehicle for solubilization and in vivo delivery of ATRA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Humans
  • Lipid Bilayers / chemistry*
  • Nanostructures / chemistry*
  • Tretinoin / administration & dosage*
  • Tretinoin / chemistry
  • Tretinoin / pharmacology

Substances

  • Lipid Bilayers
  • Tretinoin