Novel Lansoprazole-Loaded Nanoparticles for the Treatment of Gastric Acid Secretion-Related Ulcers: In Vitro and In Vivo Pharmacokinetic Pharmacodynamic Evaluation

The objective of this study is to combine nanoparticle design and enteric coating technique to sustain the delivery of an acid-labile drug, lansoprazole (LPZ), in the treatment of acid reflux disorders. Lansoprazole-loaded EudragitA (R) RS100 nanoparticles (ERSNP-LPZ) as well as poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGANP-LPZ) were prepared using a solvent evaporation/extraction method. The effects of nanoparticle charge and permeation enhancers on lansoprazole uptake was assessed in Caco-2 cells. The confocal microscopic images revealed the successful localization of nanoparticles in the cytoplasm of Caco-2 cells. The cellular uptake of positively charged Eudragit nanoparticles was significantly higher than that of negatively charged PLGA nanoparticles, which were enhanced by sodium caprate via the transcellular pathway. Both types of nanoparticles exhibited sustained drug release behavior in vitro. The oral administration of enteric-coated capsules filled with nanoparticles sustained and prolonged the LPZ concentration up to 24 h in ulcer-induced Wistar rats, and 92.4% and 89.2% of gastric ulcers healed after a 7-day treatment with either EC-ERSNP1010-Na caprate or EC-PLGANP1005-Na caprate, respectively.