Selective adhesion of nanoparticles to inflamed tissue in gastric ulcers

Pharm Res. 2009 May;26(5):1149-54. doi: 10.1007/s11095-009-9834-1. Epub 2009 Feb 10.

Abstract

Purpose: Gastrointestinal deposition of nanoparticles was examined after oral administration to mice suffering from an experimental gastric ulcer model. Local drug delivery could reduce side effects and would be a distinct improvement compared to existing therapeutic approaches, e.g. in the local therapy of Helicobacter pylori.

Methods: A gastric ulcer was induced to Swiss mice by acetic acid injection. Fluorescent polystyrene particles with a nominal size of 50, 200, and 750 nm were administered orally for 3 or 5 days and particle adhesion in the gastrointestinal tract analyzed.

Results: In the ulcerated regions, an enhanced particle adhesion was observed compared to healthy controls. A size dependency of the deposition was found which further increased with a prolonged treatment period. For 750 nm particles only fair adhesion was observed (control, 2.0 +/- 1.4%; ulcer, 4.5 +/- 0.7% of daily administered particle mass), while already 200 nm particles showed higher binding (control, 2.9 +/- 1.3%; ulcer, 7.8 +/- 1.2%). Highest relative adhesion was found for 50 nm particles (control, 2.8 +/- 1.3%; ulcer, 10.0 +/- 1.5%). The targeting index of gastric ulcer versus healthy control was nearly constant around 2 after 3 days treatment, but increased distinctly for smaller particles after 5 days.

Conclusions: The use of sub-micron sized carriers holds promise for the targeted delivery of drugs to the ulcerated mucosal areas in the stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Drug Carriers / therapeutic use
  • Fluorescent Dyes
  • Gastric Mucosa / metabolism*
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects*
  • Male
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use
  • Particle Size
  • Polystyrenes
  • Stomach / pathology
  • Stomach Ulcer / drug therapy*
  • Stomach Ulcer / pathology
  • Tissue Distribution

Substances

  • Drug Carriers
  • Fluorescent Dyes
  • Polystyrenes