Citric acid-loaded W1/O/W2 multiple emulsions efficiently remove colonic ammonia both in vitro and in vivo

Hepatic encephalopathy (HE) is a neuropsychiatric disorder caused by chronic and acute liver diseases. It is believed that ammonia played an important role on the pathogenesis of the disease. Herein, acid-loaded water-in-oil-in-water (W1/O/W2) multiple emulsions with over 95% encapsulation efficiency were prepared and used to absorb colonic ammonia. The study of citric acid release from W1 to W2 in bulk deionized water indicated that only 17% acid released in 8 hours, which proved the stability of the multiple emulsions and hence prevented the intestine from being irritated by acid burst release. In vitro, the W1/O/W2 emulsion could remove around 90% ammonia in 1.5 hours from either the 3 mmol/L ammonia solution or the artificial colonic fluid with 1 and 0.5 mmol/L ammonia without acidifying the artificial colonic fluid. In vivo, compared with lactulose, W1/O/W2 emulsions could efficiently reduce the blood ammonia to the similar level in the rat models with HE without increasing the water content in feces. All these results indicated a potential application of W1/O/W2 multiple emulsions for the treatment of HE.