Effect of paracellular permeation enhancers on intestinal permeability of two peptide drugs,enalaprilat and hexarelin, in rats

作     者：David Dahlgren Tobias Olander Markus Sjoblom Mikael Hedeland Hans Lennernas David Dahlgren;Tobias Olander;Markus Sj(o)blom;Mikael Hedeland;Hans Lennern(a)s

作者机构：Department of Pharmaceutical BiosciencesTranslational Drug Discovery and DevelopmentUppsala UniversityUppsala 75236Sweden Department of NeuroscienceDivision of PhysiologyUppsala UniversityUppsala 75236Sweden Department of Medicinal ChemistryAnalytical Pharmaceutical ChemistryUppsala UniversityUppsala 75236Sweden Department of ChemistryEnvironment and Feed HygieneNational Veterinary Institute(SVA)Uppsala 75189Sweden 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第6期

页      面：1667-1675页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100706[医学-药理学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

主　　题：Permeation enhancers Absorption-modifying excipients Oral peptide delivery Intestinal permeability Intestinal perfusion Pharmaceutical development 

摘      要：Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two *** was investigated using the rat single-pass intestinal perfusion model with concomitant blood *** luminal compositions included two paracellular permeation enhancers,chitosan(5 mg/mL) and ethylenediaminetetraacetate(EDTA,1 and 5 mg/mL),as well as low luminal tonicity(100 mOsm) with or without *** were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat,and the blood-to-lumen clearance of ^(51)chromium-labeled EDTA(CL_(Cr-EDTA)),a clinical marker for mucosal barrier *** two paracellular permeation enhancers increased the mucosal permeability of both peptide drugs to a similar *** data in this study suggests that the potential for paracellular permeability enhancers to increase intestinal absorption of hydrophilic peptides with low molecular mass is greater than for those with transcellular ***,the mucosal blood-to-lumen flux of ^(51)Cr-EDTA was increased by the two paracellular permeation enhancers and by luminal *** contrast,luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and *** suggests that hypotonicity affects paracellular solute transport primarily in the mucosal crypt region,as this area is protected from luminal contents by a constant water flow from the crypts.