Gastrointestinal lipolysis and trans-epithelial transport of SMEDDS via oral route  

作　　者：Fei Xia Zhongjian Chen Quangang Zhu 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 [2]Shanghai Skin Disease Hospital,Tongji University School of Medicine,Shanghai 200443,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第4期1010-1020,共11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：Self-microemulsifying drug delivery systems(SMEDDSs)have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules.However,information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare.Aggregation-caused quenching(ACQ)fuorescent probes are utilized to visualize the in vivo behaviors of SMEDDSs,because the released probes during lipolysis are quenched upon contacting water.Two SMEDDSs composed of medium chain triglyceride and different ratios of Tween-80 and PEG-400 are set as models,meanwhile Neoral?was used as a control.The SMEDDS droplets reside in the digestive tract for as long as 24 h and obey frst order kinetic law of lipolysis.The increased chain length of the triglyceride decreases the lipolysis of the SMEDDSs.Ex vivo imaging of main tissues and histological examination confrm the trans-epithelial transportation of the SMEDDS droplets.Approximately 2%-4%of the given SMEDDSs are transported via the lymph route following epithelial uptake,while liver is the main termination.Caco-2 cell lines confrm the cellular uptake and trans-epithelial transport.In conclusion,a fraction of SMEDDSs can survive the lipolysis in the gastrointestinal tract,permeate across the epithelia,translocate via the lymph,and accumulate mainly in the liver.

关 键 词：SMEDDS In vivo fate LIPOLYSIS Trans-epithelial transport LYMPH Aggregation-caused quenching CACO-2 Absorption 

分 类 号：R943[医药卫生—药剂学]