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intracellular uptake of nanocrystals:Probing with aggregation-induced emission of fluorescence and kinetic modeling

Acta Pharmaceutica Sinica B 2021年第4期11卷 1021-1029页

作者： Jifen Zhang Clairissa DCorpstein Tonglei Li College of Pharmaceutical Sciences Southwest UniversityChongqing 400716China Department of Industrial and Physical Pharmacy Purdue UniversityWest LafayetteIN 47907USA

Nanocrystal formulations have been explored to deliver poorly water-soluble drug *** various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocrystals at various levels,ranging from cells to tissues and to the whole *** this study,nanocrystals of tetrakis(4-hydroxyphenyl)ethylene(THPE)with an aggregation-induced emission(AIE)property was used as a model to explore intracellular absorption mechanism and dissolution kinetics of *** uptake studies were conducted with KB cells and characterized by confocal microscopy,fow cytometry,and quantitative *** results suggested that THPE nanocrystals could be taken up by KB cells directly,as well as in the form of dissolved *** cellular uptake was found to be concentration-and *** addition,the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and *** modeling was conducted to further understand the cellular mechanism of THPE nanocrystals based on frst-order ordinary differential equations(ODEs).By ftting the kinetic model against experimental measurements,it was found that the initial nanocrystal concentration had a great infuence on the dynamic process of dissolution,cellular uptake,and exocytosis of THPE *** the nanocrystal concentration increased in the culture media,dissolution of endocytosed nanocrystals became enhanced,subsequently driving the effux of THPE molecules from cells.

关键词： Nanocrystal intracellular uptake Aggregation-induced emission Pharmacokinetics Tetrakis(4-hydroxyphenyl)ethylene Fate Dissolution kinetics Absorption mechanism

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