Application of nanoparticles for oral delivery of acid-labile lansoprazole in the treatment of gastric ulcer: in vitro and in vivo evaluations.

Abstract

The aim of this study was to develop nanoparticles for oral delivery of an acid-labile drug, lansoprazole (LPZ), for gastric ulcer therapy. LPZ-loaded positively charged Eudragit(®) RS100 nanoparticles (ERSNPs-LPZ) and negatively charged poly(lactic-co-glycolic acid) nanoparticles (PLGANPs-LPZ) were prepared. The effect of charge on nanoparticle deposition in ulcerated and non-ulcerated regions of the stomach was investigated. The cellular uptake of nanoparticles in the intestine was evaluated in a Caco-2 cell model. The pharmacokinetic performance and ulcer healing response of LPZ-loaded nanoparticles following oral administration were evaluated in Wistar rats with induced ulcers. The prepared drug-loaded ERSNPs-LPZ and PLGANPs-LPZ possessed opposite surface charge (+38.5±0.3 mV versus -27.3±0.3 mV, respectively) and the particle size was around 200 nm with a narrow size distribution. The negatively charged PLGANPs adhered more readily to the ulcerated region (7.22%±1.21% per cm(2)), whereas the positively charged ERSNPs preferentially distributed in the non-ulcerated region (8.29%±0.35% per cm(2)). Both ERSNPs and PLGANPs were prominent uptake in Caco-2 cells, too. The nanoparticles sustained and prolonged LPZ concentrations up to 24 hours, and the half-life and mean residence time of LPZ were prolonged by 3.5-fold and 4.5-fold, respectively, as compared with LPZ solution. Oral administration of LPZ-loaded nanoparticles healed 92.6%-95.7% of gastric ulcers in Wistar rats within 7 days.

• Authors: Milind Alai, Wen Jen Lin
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 10 Pg. 4029-41 ( 2015) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 26124659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Ulcer Agents
• Lansoprazole

Topics

• Administration, Oral
• Animals
• Anti-Ulcer Agents (administration & dosage, therapeutic use)
• Caco-2 Cells
• Humans
• Lansoprazole (administration & dosage, therapeutic use)
• Nanoparticles (administration & dosage, chemistry)
• Rats
• Rats, Wistar
• Stomach Ulcer (drug therapy)