title: [Esterase activity of human organotypic cornea construct (HCC) as in vitro model for permeation studies].
abstract: Organotypic cornea equivalents are used as in vitro models for permeation studies. Many ophthalmic drugs are applied as ester prodrugs to achieve a higher bioavailability. The esterase activity of three corneal human cell lines (epithelial, stromal, endothelial cells) as well as of excised porcine cornea, human donor cornea and human cornea construct (HCC) was investigated and compared. Esterase activity was determined using p-nitrophenyl acetate and hydrocortisone acetate (HCA) as esterase substrates. Hydrocortisone acetate permeation across porcine cornea, human donor cornea and HCC was studied in vitro using Franz-diffusion cells. Corneal epithelial cells showed the highest esterase activity and only small differences to keratocytes and endothelial cells were detectable. The permeation barrier properties of the different corneal tissues were very similar in the case of HCA permeation whereas HCA metabolism rates were in the ranking order of porcine cornea > HCC > human donor cornea. Permeation and metabolism studies indicate that the in vitro permeation model HCC is able to adequately convert hydrocortisone acetate to hydrocortisone.
authors.affiliation: Institut für Pharmazeutische Technologie der Technischen Universität Braunschweig.
authors.forename: L
authors.initials: L
authors.lastname: Meyer
authors.forename: J
authors.initials: J
authors.lastname: Bednarz
authors.forename: C C
authors.initials: CC
authors.lastname: Müller-Goymann
authors.forename: S
authors.initials: S
authors.lastname: Reichl
mesh_terms: D000368:Aged; D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003319:Corneal Stroma / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004728:Endothelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004950:Esterases / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics*; D009924:Organ Culture Techniques; D010539:Permeability; D011355:Prodrugs / Q000493:pharmacokinetics; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D009883:Ophthalmic Solutions; D011355:Prodrugs; C021650:hydrocortisone acetate; D004950:Esterases; D006854:Hydrocortisone