title: 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.affiliation: Graduate Institute of Pharmaceutical Sciences, School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Milind
authors.initials: M
authors.lastname: Alai
authors.affiliation: Graduate Institute of Pharmaceutical Sciences, School of Pharmacy, National Taiwan University, Taipei, Taiwan ; Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen Jen
authors.initials: WJ
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018938:Caco-2 Cells; D006801:Humans; D064747:Lansoprazole / Q000008:administration & dosage / Q000627:therapeutic use; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy*
chemical_list: D000897:Anti-Ulcer Agents; D064747:Lansoprazole
keywords: Eudragit® RS100; PLGA; lansoprazole; nanoparticles