Original articles
Fei Xia, Zhongjian Chen, Quangang Zhu, Jianping Qi, Xiaochun Dong, Weili Zhao, Wei Wu, Yi Lu. Gastrointestinal lipolysis and trans-epithelial transport of SMEDDS via oral route[J]. Acta Pharmaceutica Sinica B, 2021, 11(4): 1010-1020

Gastrointestinal lipolysis and trans-epithelial transport of SMEDDS via oral route
Fei Xiaa, Zhongjian Chenb, Quangang Zhub, Jianping Qia, Xiaochun Donga, Weili Zhaoa, Wei Wua, Yi Lua
a Key Laboratory of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai 201203, China;
b Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China
Abstract:
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) fluorescent 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 first 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 confirm 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 confirm 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.
Key words:    SMEDDS    In vivo fate    Lipolysis    Trans-epithelial transport    Lymph    Aggregation-caused quenching    Caco-2    Absorption   
Received: 2020-10-08     Revised: 2020-12-31
DOI: 10.1016/j.apsb.2021.03.006
Funds: This work was supported by the National Natural Science Foundation of China (Nos. 82030107, 81973247, 81872815, 81872826, and 81690263) and Science and Technology Commission of Shanghai Municipality (Nos. 19XD1400300, 19430741400, and 19410761200, China).
Corresponding author: Yi Lu, fd_luyi@fudan.edu.cn     Email:fd_luyi@fudan.edu.cn
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Fei Xia
Zhongjian Chen
Quangang Zhu
Jianping Qi
Xiaochun Dong
Weili Zhao
Wei Wu
Yi Lu

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