Ionic co-aggregates(ICAs)based oral drug delivery:Solubilization and permeability improvement  

作　　者：Xianzi Zheng Zhezheng Fang Weizi Huang Jianping Qi Xiaochun Dong Weili Zhao Wei Wu Yi Lu 

机构地区：[1]Key Laboratory of Smart Drug Delivery of MOE,School of Pharmacy,Fudan University,Shanghai 201203,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第10期3972-3985,共14页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.82030107,81973247,81872815,81872826,and 81690263);Science and Technology Commission of Shanghai Municipality(Nos.19XD1400300,19430741400,and 19410761200,China).

摘　　要：Due to the overwhelming percentage of poorly water-soluble drugs,pharmaceutical industry is in urgent need of efficient approaches for solubilization and permeability improvement.Salts consisting of lipophilic fatty acid anions and hydrophilic choline cations are found to be surface active and able to form ionic co-aggregates(ICAs)in water.Choline oleate-based ICAs significantly enhance oral absorption of paclitaxel(PTX)as compared with cremophor EL-based micelles(MCs).Aggregation-caused quenching probes enable tracking of intact ICAs in in vivo transport and cellular interaction.Prolonged intestinal retention of ICAs than MCs implies stronger solubilizing capability in vivo.Ex vivo imaging of major organs and intestinal tracts suggests transepithelial transport of intact ICAs.Cellular studies support the enhanced absorption of PTX and transmembrane transport of intact ICAs.In conclusion,ICAs,consisting of lipophilic ions and hydrophilic counter-ions,are of great potential in delivery of poorly water-soluble drugs by enhancing solubility and permeability.

关 键 词：Ionic co-aggregates Molecular dynamics simulation Oral BIOAVAILABILITY Aggregation-caused quenching PACLITAXEL In vivo fate CACO-2 

分 类 号：R943[医药卫生—药剂学]