Doctoral candidate
Pharmacist
Contact
Institut für Pharmazeutische Technologie und Biopharmazie
Technische Universität Braunschweig
Mendelssohnstraße 1
38106 Braunschweig
E-Mail: michelle.duettmann(at)tu-braunschweig.de
Room: 137
Telephone: +49 531 391-5640
PVZ / Dep. 4
Room: 359
Telephone: +49 531 391-65653
Field of work
Ocular DynaMiTES - In vitro/in vivo correlation of a dynamised tissue model of the cornea in the pharmacokinetic testing of ophthalmic drugs
Active ingredients in ophthalmic preparations are generally absorbed transcorneally and thus reach the aqueous humour via the cornea. The bioavailability of ophthalmic drugs is very low. Preclinical studies on pharmacokinetics or bioequivalence are therefore of great relevance in the development of new ophthalmic formulations and generics. These are currently still predominantly carried out in animal experiments, which are ethically questionable and whose results cannot be reliably transferred to humans. Therefore, in this project the already established in vitro test system Ocular DynaMiTES (Dynamic Micro Tissue Engineering System) [1-8] is prevalidated as an alternative method. The focus of this work is on an in vitro/in vivo correlation with regard to the permeation of ophthalmological active substances from different formulations and the determination of the discriminatory power of the method. In addition, the applicability of the system for in vitro bioequivalence testing is analysed and the robustness of the method is determined.
Funded by BMBF
FKZ: 16LW0332
References
[1] Mattern K, Beißner N, Reichl S, et al. (2018) DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 1 - Engineering of microfluidic system and technical simulations. Eur J Pharm Biopharm 126:159–165
[2] Beiβner N, Mattern K, Dietzel A, et al. (2018) DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 2 - Ocular DynaMiTES for drug absorption studies of the anterior eye. Eur J Pharm Biopharm 126:166–176
[3] Lorenz T, Kirschke M, Ledwig V, et al. (2021) Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles. Bioengineering (Basel) 8
[4] Hahne M, Reichl S (2011) Development of a serum-free human cornea construct for in vitro drug absorption studies: the influence of varying cultivation parameters on barrier characteristics. Int J Pharm 416:268–279
[5] Hahne M, Zorn-Kruppa M, Guzman G, et al. (2012) Prevalidation of a human cornea construct as an alternative to animal corneas for in vitro drug absorption studies. J Pharm Sci 101:2976–2988
[6] Kölln C, Reichl S (2012) mRNA expression of metabolic enzymes in human cornea, corneal cell lines, and hemicornea constructs. J Ocul Pharmacol Ther 28:271–277
[7] Kölln C, Reichl S (2016) Cytochrome P450 Activity in Ex Vivo Cornea Models and a Human Cornea Construct. J Pharm Sci 105:2204–2212
[8] Kölln C, Reichl S (2016) Expression of glutathione transferases in corneal cell lines, corneal tissues and a human cornea construct. Int J Pharm 506:371–381