Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles

Int J Nanomedicine. 2013:8:2709-17. doi: 10.2147/IJN.S47400. Epub 2013 Jul 29.

Abstract

Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L, which has high water solubility and low oral bioavailability. This research aims to develop a hydrophobic nanoparticle that can enhance the oral absorption of HSYA. Transmission electron microscopy and freeze-fracture replication transmission election microscopy showed that the HSYA nanoparticles have an irregular shape and a narrow size distribution. Zonula occludens 1 protein (ZO-1) labeling showed that the nanoparticles with different dilutions produced an opening in the tight junctions of Caco-2 cells without inducing cytotoxicity to the cells. Both enhanced uptake in Caco-2 cells monolayer and increased bioavailability in rats for HSYA nanoparticles indicated that the formulation could improve bioavailability of HSYA significantly after oral administration both in vitro and in vivo.

Keywords: Caco-2 cells; absorption; bioavailability; hydroxysafflor yellow A; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption / drug effects*
  • Administration, Intravenous
  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Biological Availability
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Chalcone / administration & dosage
  • Chalcone / analogs & derivatives*
  • Chalcone / blood
  • Chalcone / chemistry
  • Chalcone / pharmacokinetics
  • Chalcone / pharmacology
  • Endocytosis / drug effects
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Male
  • Nanoparticles / chemistry*
  • Quinones / administration & dosage
  • Quinones / blood
  • Quinones / chemistry
  • Quinones / pharmacokinetics*
  • Quinones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Quinones
  • Zonula Occludens-1 Protein
  • hydroxysafflor yellow A
  • Chalcone