title: The addition of a pH-sensitive gel improves microemulsion stability for the targeted removal of colonic ammonia.
abstract: BACKGROUND
  We prepared an oral W/O microemulsion for the removal of colonic ammonia (ME-RCA). The effect of this microemulsion was influenced by the digestion process in the gastrointestinal tract. In this paper, we aim to show that stability was improved by using a microemulsion-based gel for the removal of colonic ammonia (MBG-RCA).
  
  
  METHODS
  MBG-RCA was prepared by adding sodium alginate to the ME-RCA. MBG-RCA and ME-RCA were passed through a simulated gastrointestinal environment, and the amount of colonic ammonia present was then determined by titration with a standard solution of hydrochloric acid. The pH of the gastrointestinal fluid was measured using a pH test paper and the size and form of the microemulsions were examined under the microscope. 18 healthy rats were randomly divided into three groups, fasted for 24 hours and allowed to drink normally. Three-way pipes were placed at the gastroduodenal junction in Group I, and at the terminal ileum in Group II. After the intragastric administration of ME-RCA, the stomach contents in Group I, the effluent from the terminal ileum in Group II and discharge from the anus in Group III were collected. The pH values of the gastrointestinal juice were measured by the pH test paper and those of the colon were determined by a universal indicator. These animal experiments were also used to test the effect of MBG-RCA.
  
  
  RESULTS
  MBG-RCA showed a better removal rate of artificial colonic ammonia than ME-RCA (P < 0.05). The decrease in pH value of the artificial small intestinal fluid due to ME-RCA did not occur when MBG-RCA was used. In the simulated gastrointestinal process, MBG-RCA maintained greater stability and released the emulsion (ME-RCA) in the colonic fluid. In the gastrointestinal tract of normal SD rats, ME-RCA decreased in size and lost its stable form after entering the small intestine, while MBG-RCA remained stable and intact emulsion-drops were observed from the anus. Neither substance had any effect on the pH of the stomach or colon of normal rats (partly because normal rats were fasted for 24 hours and allowed to drink normally, which resulted in a low level of ammonia production in the colon). Unlike ME-RCA, MBG-RCA did not reduce the pH of the small intestine.
  
  
  CONCLUSIONS
  MBG-RCA was more stable in the gastrointestinal tract and more effective at removing colonic ammonia when a higher concentration of ammonia was present. This made it possible to achieve the targeted removal of colonic ammonia and is a promising method to prevent hepatic encephalopathy (HE) in future studies.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian 0086-116011, Liaoning Province, China.
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Wang
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Duan
authors.forename: Ge
authors.initials: G
authors.lastname: Tian
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Gao-Hong
authors.initials: GH
authors.lastname: He
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Fang
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000641:Ammonia / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D003106:Colon / Q000737:chemistry*; D004355:Drug Stability; D004655:Emulsions; D005750:Gastric Juice / Q000737:chemistry; D005766:Gastrointestinal Contents / Q000737:chemistry; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007421:Intestine, Small / Q000737:chemistry; D008657:Metabolic Clearance Rate; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000737:chemistry
chemical_list: D000464:Alginates; D004655:Emulsions; D005782:Gels; D006603:Hexuronic Acids; D004364:Pharmaceutical Preparations; D000641:Ammonia; D020723:Glucuronic Acid