Permeability profiles and intestinal toxicity assessment of hydrochlorothiazide and its inclusion complex with β-cyclodextrin loaded into chitosan nanoparticles

ONNAINTY RENEE; SCHENFELD ESTEBAN; PETITI J.; LONGHI MARCELA; QUEVEDO MARIO ALFREDO; GRANERO G.

MOLECULAR PHARMACEUTICS

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 13 p. 3736 - 3736

1543-8384

ere, a novel drug delivery system was developed for the hydrochlorothiazide(HCT):β-cyclodextrin (βCD) inclusion complex loaded into chitosan (CS) nanoparticles(NPs) [CS/HCT:βCD NPs]. It was found, for the first time, that exposure of the intestinalmucosa to free HCT resulted in an increased and abnormal intestinal permeability associatedwith several injuries to the intestinal epithelium. Nevertheless, the HCT delivery systemobtained ameliorated the damage of the intestinal epithelium induced by HCT. Furthermore,we found that the corresponding permeability profiles for both the free HCT and the CS/HCT:βCD NPs were exponential and lineal, respectively. We propose that the increasedintestinal uptake and severe tissue injury of HCT to the intestinal epithelium could bedirectly related to possible effects of this drug on the ionoregulatory Na+/K+-ATPase channel.Thus, it is postulated that the CS/HCT:βCD NPs may increase the gastrointestinal retentionof the HCT, whi