Beclomethasone dipropionate-loaded colon-targeting UniORV® for effective treatment of colitis

Abstract

This study was undertaken to develop novel colon-targeting UniORV® (cUO) of beclomethasone dipropionate (BDP) for strategic oral delivery to the disease site of colitis. BDP-loaded cUO (cUO/BDP) was characterized regarding morphology and dissolution behaviors. Plasma levels of beclomethasone 17-monopropionate (17-BMP), a metabolite of BDP, were measured after oral administration of BDP samples to rats. Anti-inflammatory effects of oral BDP samples (50 μg-BDP/kg) were assessed in a rat model of colitis. The cUO/BDP was found to be a 300 μm-sized spherical particle. Compared with crystalline BDP, cUO/BDP exhibited a marked improvement in dissolution behavior only under colonic conditions, and the dissolution of BDP from cUO was negligible under upper gastrointestinal conditions. Oral BDP solution (5 mg-BDP/kg) led to a rapid increase in the plasma 17-BMP level with a maximum plasma concentration (Cmax) as high as 620 ng/mL and time to Cmax of 0.9 h. In contrast, Cmax of oral cUO/BDP was below 5 ng/mL, suggesting suppressed upper gastrointestinal absorption and enhanced delivery to the colon. In the rat model of colitis, compared with BDP solution, oral cUO/BDP significantly attenuated neutrophilia in the colon. The use of cUO may be a promising strategy to enhance the efficacy of BDP against colitis.