pH-sensitive nanoparticles for colonic delivery of curcumin in inflammatory bowel disease

Abstract

Nano-scaled particles have been found to preferentially accumulate in inflamed regions. Local delivery of anti-inflammatory drugs loaded in nanoparticles to the inflamed colonic site is of great interest for inflammatory bowel disease (IBD) treatment. Curcumin (CC) is an anti-inflammatory local agent, which presents poor ADME properties. Hence, we evaluated, both in vitro and in vivo, the local delivery of CC using pH-sensitive polymeric nanoparticles (NPs) combining both poly(lactide-co-glycolide) acid (PLGA) and a polymethacrylate polymer (Eudragit(®) S100). CC-NPs significantly enhanced CC permeation across Caco-2 cell monolayers when compared to CC in suspension. CC-NPs significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, CC-NPs significantly decreased neutrophil infiltration and TNF-α secretion while maintaining the colonic structure similar to the control group in a murine DSS-induced colitis model. Our results support the use of nanoparticles made of PLGA and Eudragit(®) S100 combination for CC delivery in IBD treatment.

Keywords: Curcumin; Eudragit(®); Inflammatory bowel disease; Nanoparticles; PLGA; pH-sensitive.