Prevalidation of a human cornea construct as an alternative to animal corneas for in vitro drug absorption studies.
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Prevalidation of a human cornea construct as an alternative to animal corneas for in vitro drug absorption studies. / Hahne, Matthias; Zorn-Kruppa, Michaela; Guzman, Gustavo; Brandner, Johanna; Haltner-Ukomado, Eleonore; Wätzig, Hermann; Reichl, Stephan.
In: J PHARM SCI-US, Vol. 101, No. 8, 8, 2012, p. 2976-2988.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prevalidation of a human cornea construct as an alternative to animal corneas for in vitro drug absorption studies.
AU - Hahne, Matthias
AU - Zorn-Kruppa, Michaela
AU - Guzman, Gustavo
AU - Brandner, Johanna
AU - Haltner-Ukomado, Eleonore
AU - Wätzig, Hermann
AU - Reichl, Stephan
PY - 2012
Y1 - 2012
N2 - The use of ophthalmic drugs has increased consistently over the past few decades. Currently, most research is conducted using in vivo and ex vivo animal experiments; however, they have many disadvantages, including ethical concerns, high costs, the questionable extension of animal results to humans, and poor standardization. Although several cell culture-based cornea models have been developed, none have been validated and accepted for general use. In this study, a standardized, three-dimensional model of the human cornea (Hemicornea, HC) based on immortalized human corneal cells and cultivated in serum-free conditions was developed for drug absorption studies and prevalidated using compounds with a wide range of molecular characteristics (sodium fluorescein, rhodamine B, fluorescein isothiocyanate-labeled dextran, aciclovir, bimatoprost, dexamethasone, and timolol maleate). The HC model was independently cultured in three different laboratories, and the intralaboratory and interlaboratory reproducibility was analyzed and compared with the rabbit cornea. This analysis showed that the HC has a barrier in the same range as excised animal corneas, although with a higher reproducibility and lower variability. Because of the demonstrated transferability, the HC represents a promising in vitro alternative to the use of ex vivo tissue and offers a well-defined and standardized system for drug absorption studies.
AB - The use of ophthalmic drugs has increased consistently over the past few decades. Currently, most research is conducted using in vivo and ex vivo animal experiments; however, they have many disadvantages, including ethical concerns, high costs, the questionable extension of animal results to humans, and poor standardization. Although several cell culture-based cornea models have been developed, none have been validated and accepted for general use. In this study, a standardized, three-dimensional model of the human cornea (Hemicornea, HC) based on immortalized human corneal cells and cultivated in serum-free conditions was developed for drug absorption studies and prevalidated using compounds with a wide range of molecular characteristics (sodium fluorescein, rhodamine B, fluorescein isothiocyanate-labeled dextran, aciclovir, bimatoprost, dexamethasone, and timolol maleate). The HC model was independently cultured in three different laboratories, and the intralaboratory and interlaboratory reproducibility was analyzed and compared with the rabbit cornea. This analysis showed that the HC has a barrier in the same range as excised animal corneas, although with a higher reproducibility and lower variability. Because of the demonstrated transferability, the HC represents a promising in vitro alternative to the use of ex vivo tissue and offers a well-defined and standardized system for drug absorption studies.
KW - Animals
KW - Humans
KW - Female
KW - Rabbits
KW - Cell Line
KW - Swine
KW - Cell Culture Techniques
KW - Administration, Ophthalmic
KW - Epithelium, Corneal/cytology/metabolism/ultrastructure
KW - Ophthalmic Solutions/administration & dosage
KW - Pharmaceutical Preparations/administration & dosage
KW - Pharmacokinetics
KW - Animals
KW - Humans
KW - Female
KW - Rabbits
KW - Cell Line
KW - Swine
KW - Cell Culture Techniques
KW - Administration, Ophthalmic
KW - Epithelium, Corneal/cytology/metabolism/ultrastructure
KW - Ophthalmic Solutions/administration & dosage
KW - Pharmaceutical Preparations/administration & dosage
KW - Pharmacokinetics
M3 - SCORING: Journal article
VL - 101
SP - 2976
EP - 2988
JO - J PHARM SCI-US
JF - J PHARM SCI-US
SN - 0022-3549
IS - 8
M1 - 8
ER -
