DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 2-Ocular DynaMiTES for drug absorption studies of the anterior eye

被引:28
作者
Beissner, Nicole [1 ,3 ]
Mattern, Kai [2 ,3 ]
Dietzel, Andreas [2 ,3 ]
Reichl, Stephan [1 ,3 ]
机构
[1] Tech Univ Carolo Wilhelmina Braunschweig, Inst Pharmazeut Technol, Mendelssohnstr 1, D-38106 Braunschweig, Germany
[2] Tech Univ Carolo Wilhelmina Braunschweig, Inst Mikrotech, Alte Salzdahlumer Str 203, D-38124 Braunschweig, Germany
[3] Tech Univ Carolo Wilhelmina Braunschweig, Ctr Pharmaceut Engn PVZ, Franz Liszt Str 35 A, D-38106 Braunschweig, Germany
关键词
DynaMiTES; Human hemicornea construct; Microfluidic system; Organ on chip; TEER measurement; Dynamic flow system; In vitro drug absorption; Benzalkonium chloride; HUMAN CORNEA CONSTRUCT; BENZALKONIUM CHLORIDE; MODELS; PERMEABILITY; EXPRESSION; BARRIER; CHIP; PRESERVATIVES; CULTIVATION; DELIVERY;
D O I
10.1016/j.ejpb.2017.03.021
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In the present study, a formerly designed Dynamic Micro Tissue Engineering System (DynaMiTES) was applied with our prevalidated human hemicornea (HC) construct to obtain a test platform for improved absorption studies of the anterior eye (Ocular DynaMiTES). First, the cultivation procedure of the classic HC was slightly adapted to the novel DynaMiTES design. The obtained inverted HC was then compared to classic HC regarding cell morphology using light and scanning electron microscopy, cell viability using MIT dye reaction and epithelial barrier properties observing transepithelial electrical resistance and apparent permeation coefficient of sodium fluorescein. These tested cell criteria were similar. In addition, the effects of four different flow rates on the same cell characteristics were investigated using the DynaMiTES. Because no harmful potential of flow was found, dynamic absorption studies of sodium fluorescein with and without 0.005%, 0.01% and 0.02% benzalkonium chloride were performed compared to the common static test procedure. In this proof-of-concept study, the dynamic test conditions showed different results than the static test conditions with a better prediction of in vivo data. Thus, we propose that our DynaMiTES platform provides great opportunities for the improvement of common in vitro drug testing procedures. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:166 / 176
页数:11
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