In vitro cell culture models to study the corneal drug absorption

Expert Opinion on Drug Metabolism and Toxicology

Volumn 7, Issue 5, 2011, Pages 559-578

  Reichl, Stephan ^a   Kölln, Christian ^a   Hahne, Matthias ^a   Verstraelen, Jessica ^a  

^a TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

Author keywords

3D corneal equivalents; active drug transport; corneal barrier; corneal cell lines; drug absorption; in vitro models; metabolism

Indexed keywords

ACEBUTOLOL; ACICLOVIR; ADEFOVIR; ALANINE; AMANTADINE; BENZOIC ACID; CARNITINE; CEFALEXIN; CIMETIDINE; CYCLOSPORIN A; DESIPRAMINE; DIGOXIN; ERYTHROMYCIN; ETOPOSIDE; GANCICLOVIR; GLYCYLSARCOSINE; INDINAVIR; LACTIC ACID; LATANOPROST; METHOTREXATE; PHENYLALANINE; QUINIDINE; QUINIDINE DERIVATIVE; RHODAMINE; RITONAVIR; TILISOLOL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALACICLOVIR; VALQUINIDINE; VERAPAMIL;

BASAL CELL; BOWMAN MEMBRANE; CELL CULTURE; CORNEA; DRUG ABSORPTION; DRUG ACTIVITY; DRUG PENETRATION; DRUG TRANSPORT; ENDOTHELIUM; EPITHELIUM; HUMAN; IN VITRO STUDY; MOLECULAR MODEL; NONHUMAN; REVIEW; STROMA;

ADMINISTRATION, TOPICAL; ANIMAL TESTING ALTERNATIVES; ANIMALS; CELL CULTURE TECHNIQUES; CORNEA; EPITHELIUM, CORNEAL; EYE DISEASES; HUMANS; MODELS, BIOLOGICAL; PERMEABILITY; PHARMACEUTICAL PREPARATIONS;

ANIMALIA;

EID: 79955094804     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.2011.562195     Document Type: Review

References (154)

1. Jarvinen K, Jarvinen T, Urtti A. Ocular absorption following topical delivery. Adv Drug Deliv Rev 1995;16:3-19
2. Barar J, Javadzadeh AR, Omidi Y. Ocular novel drug delivery: impacts of membranes and barriers. Expert Opin Drug Deliv 2008;5:567-81 (Pubitemid 351877434)
3. Hornof M, Toropainen E, Urtti A. Cell culture models of the ocular barriers. Eur J Pharm Biopharm 2005;60:207-25 (Pubitemid 40804562)
4. Reichl S, Becker U. Cell culture models of the corneal epithelium and reconstructed cornea equivalents for in vitro drug absorption studies. In: Ehrhardt C, Kim KJ, editors, Drug absorption studies - In situ, in vitro and in silico models. 1st edition. Springer, New York; 2008. p. 283-306
5. Klyce S, Beuermann R. Structure and function of the cornea. In: Kaufman H, Barron B, McDonald M, editors, The cornea. 2nd edition. Butterworth- Heinemann, Boston; 1998. p. 3-50
6. Beuerman RW, Pedroza L. Ultrastructure of the human cornea. Microsc Res Tech 1996;33:320-35 (Pubitemid 26068260)
7. Schoenwald RD. Ocular drug delivery. Pharmacokinetic considerations. Clin Pharmacokinet 1990;18:255-69 (Pubitemid 20134535)
8. Davies NM. Biopharmaceutical considerations in topical ocular drug delivery. Clin Exp Pharmacol Physiol 2000;27:558-62 (Pubitemid 30418006)
9. Chen L, Ebihara N, Fujiki K, Murakami A. Expression and distribution of junctional adhesion molecule-1 in the human cornea. Jpn J Ophthalmol 2007;51:405-11
10. Sosnova-Netukova M, Kuchynka P, Forrester JV. The suprabasal layer of corneal epithelial cells represents the major barrier site to the passive movement of small molecules and trafficking leukocytes. Br J Ophthalmol 2007;91:372-8 (Pubitemid 46586538)
11. Klyce SD, Crosson CE. Transport processes across the rabbit corneal epithelium: a review. Curr Eye Res 1985;4:323-31 (Pubitemid 15123153)
12. Rojanasakul Y, Wang LY, Bhat M, et al. The transport barrier of epithelia: a comparative study on membrane permeability and charge selectivity in the rabbit. Pharm Res 1992;9:1029-34
13. Kikuchi T, Suzuki M, Kusia A, et al. Synergistic effect of EDTA and boric acid on corneal penetration of CS-088. Int J Pharm 2005;290:83-9 (Pubitemid 40139047)
14. Nakamura T, Yamada M, Teshima M, et al. Electrophysiological characterization of tight junctional pathway of rabbit cornea treated with ophthalmic ingredients. Biol Pharm Bull 2007;30:2360-4 (Pubitemid 350223743)
15. Chetoni P, Burgalassi S, Monti D, Saettone MF. Ocular toxicity of some corneal penetration enhancers evaluated by electrophysiology measurements on isolated rabbit corneas. Toxicol In Vitro 2003;17:497-504 (Pubitemid 36776791)
16. Becker U, Ehrhardt C, Schneider M, et al. A comparative evaluation of corneal epithelial cell cultures for assessing ocular permeability. ATLA 2008;36:33-44 (Pubitemid 351439797)
17. Marshall WS, Klyce SD. Cellular and paracellular pathway resistances in the tight Cl-secreting epithelium of rabbit cornea. J Membr Biol 1983;73:275-82 (Pubitemid 13061749)
18. Prausnitz MR, Noonan JS. Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye. J Pharm Sci 1998;87:1479-88
19. Mannermaa E, Vellonen KS, Urtti A. Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev 2006;58:1136-63
20. Dey S, Anand BS, Patel J, Mitra AK. Transporters/receptors in the anterior chamber: pathways to explore ocular drug delivery strategies. Expert Opin Biol Ther 2003;3:23-44 (Pubitemid 36193649)
21. Dey S, Patel J, Anand BS, et al. Molecular evidence and functional expression of P-Glycoprotein (MDR1) in human and rabbit cornea and corneal epithelial cell lines. Invest Ophthalmol Vis Sci 2003;44:2909-18 (Pubitemid 36759752)
22. Vellonen KS, Mannermaa E, Turner H, et al. Effluxing ABC transporters in human corneal epithelium. J Pharm Sci 2010;99:1087-98
23. Duvvuri S, Majumdar S, Mitra AK. Role of metabolism in ocular drug delivery. Curr Drug Metab 2004;5:507-15 (Pubitemid 39534495)
24. Thygeson P. Cultivation in vitro of human conjunctival and corneal epithelium. Am J Ophthalmol 1939;22:649-54
25. Bulow N, Ehlers N. Morphology and DOPA reaction of cultivated corneal epithelial cells. Acta Ophthalmol (Copenh) 1968;46:749-56
26. Newsome DA, Takasugi M, Kenyon KR, et al. Human corneal cells in vitro: morphology and histocompatibility (HL-A) antigens of pure cell populations. Invest Ophthalmol 1974;13:23-32
27. Gipson IK, Grill SM. A technique for obtaining sheets of intact rabbit corneal epithelium. Invest Ophthalmol Vis Sci 1982;23:269-73 (Pubitemid 12051508)
28. Ebato B, Friend J, Thoft RA. Comparison of limbal and peripheral human corneal epithelium in tissue culture. Invest Ophthalmol Vis Sci 1988;29:1533-7
29. Chang JE, Basu SK, Lee VHL. Air-interface condition promotes the formation of tight corneal epithelial cell layers for drug transport studies. Pharm Res 2000;17:670-6 (Pubitemid 30670631)
30. Kawazu K, Shiono H, Tanioka H, et al. Beta-adrenergic antagonist permeation across cultured rabbit corneal epithelial cells grown on permeable supports. Curr Eye Res 1998;17:125-31 (Pubitemid 28073776)
31. Kawazu K, Midori Y, Ota A. Cultured rabbit corneal epithelium elicits levofloxacin absorption and secretion. J Pharm Pharmacol 1999;51:791-6 (Pubitemid 29377950)
32. Kawazu K, Yamada K, Nakamura M, Ota A. Characterization of cyclosporin A transport in cultured rabbit corneal epithelial cells: P-Glycoprotein transport activity and binding to cyclophilin. Invest Ophthalmol Vis Sci 1999;40:1738-44 (Pubitemid 29297149)
33. Sakanaka K, Kawazu K, Nishida K, et al. Transport of timolol and tilisolol in rabbit corneal epithelium. Biol Pharm Bull 2006;29:2143-7 (Pubitemid 44510826)
34. Scholz M, Lin JE, Lee VH, Keipert S. Pilocarpine permeability across ocular tissues and cell cultures: influence of formulation parameters. J Ocul Pharmacol Ther 2002;18:455-68 (Pubitemid 37420254)
35. Becker U, Ehrhardt C, Schaefer UF, et al. Tissue distribution of moxaverine-hydrochloride in the rabbit eye and plasma. J Ocul Pharmacol Ther 2005;21:210-16 (Pubitemid 40934699)
36. Chang-Lin JE, Kim KJ, Lee VH. Characterization of active ion transport across primary rabbit corneal epithelial cell layers (RCrECL) cultured at an air-interface. Exp Eye Res 2005;80:827-36 (Pubitemid 40798048)
37. Meller D, Pires RT, Tseng SCG. Ex vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane cultures. Br J Ophthalmol 2002;86:463-71 (Pubitemid 34293299)
38. Reichl S. Cell culture models of the human cornea - A comparative evaluation of their usefulness to determine ocular drug absorption in vitro. J Pharm Pharmacol 2008;60:299-307 (Pubitemid 351269816)
39. Katragadda S, Talluri RS, Pal D, Mitra AK. Identification and characterization of a Na+-dependent neutral amino acid transporter, ASCT1, in rabbit corneal epithelial cell culture and rabbit cornea. Curr Eye Res 2005;30:989-1002 (Pubitemid 43154693)
40. Garrett Q, Xu S, Simmons PA, et al. Expression and localization of carnitine/organic cation transporter OCTN1 and OCTN2 in ocular epithelium. Invest Ophthalmol Vis Sci 2008;49:4844-9
41. Vellonen KS, Hakli M, Merezhinskaya N, et al. Monocarboxylate transport in human corneal epithelium and cell lines. Eur J Pharm Sci 2010;39:241-7
42. Kawazu K, Oshita A, Nakamura T, et al. Transport of acebutolol through rabbit corneal epithelium. Biol Pharm Bull 2006;29:846-9
43. Dey S, Gunda S, Mitra AK. Pharmacokinetics of erythromycin in rabbit cornea after single-dose infusion: role of P-Glycoprotein as a barrier to in vivo ocular drug absorption. J Pharmacol Exp Ther 2004;311:246-55 (Pubitemid 39287804)
44. Hariharan S, Minocha M, Mishra GP, et al. Interaction of ocular hypotensive agents (PGF2alpha analogs - bimatoprost, latanoprost, and travoprost) with MDR efflux pumps on the rabbit cornea. J Ocul Pharmacol Ther 2009;25:487-97
45. Hariharan S, Gunda S, Mishra GP, et al. Enhanced corneal absorption of erythromycin by modulating p-glycoprotein and MRP mediated efflux with corticosteroids. Pharm Res 2009;26:1270-82
46. Katragadda S, Talluri R, Mitra AK. Modulation of p-glycoprotein-mediated efflux by prodrug derivatization: an approach involving peptide transporter-mediated influx across rabbit cornea. J Ocul Pharmacol Ther 2006;22:110-20 (Pubitemid 43742947)
47. Karla P, Pal D, Quinn T, Mitra AK. Molecular evidence and functional expression of a novel drug efflux pump (ABCC2) in human corneal epithelium and rabbit cornea and its role in ocular drug efflux. Int J Pharm 2007;336:12-21 (Pubitemid 46551552)
48. Karla PK, Pal D, Mitra AK. Molecular evidence and functional expression of multidrug resistance associated protein (MRP) in rabbit corneal epithelial cells. Exp Eye Res 2007;84:53-60 (Pubitemid 44792052)
49. Karla PK, Quinn TL, Herndon BL, et al. Expression of multidrug resistance associated protein 5 (MRP5) on cornea and its role in drug efflux. J Ocul Pharmacol Ther 2009;25(2):121-32
50. Cao L, Zhang XD, Liu X, et al. Chloride channels and transporters in human corneal epithelium. Exp Eye Res 2010;90:771-9
51. Araki K, Ohashi Y, Sasabe T, et al. Immortalization of rabbit corneal epithelial cells by a recombinant SV40-adenovirus vector. Invest Ophthalmol Vis Sci 1993;34:2665-71 (Pubitemid 23232475)
52. Burgalassi S, Monti D, Brignoccoli A, et al. Development of cultured rabbit corneal epithelium for drug permeation studies: a comparison with excised rabbit cornea. J Ocul Pharmacol Ther 2004;20:518-32 (Pubitemid 39628497)
53. Di Colo G, Burgalassi S, Zambito Y, et al. Effects of different N-trimethyl chitosans on in vitro/in vivo ofloxacin transcorneal permeation. J Pharm Sci 2004;93:2851-62 (Pubitemid 39506634)
54. Gokce EH, Sandri G, Bonferoni MC, et al. Cyclosporine A loaded SLNs: evaluation of cellular uptake and corneal cytotoxicity. Int J Pharm 2008;364:76-86
55. Yang H, Reinach PS, Koniarek JP, et al. Fluid transport by cultured corneal epithelial cell layers. Br J Ophthalmol 2000;84:199-204 (Pubitemid 30251666)
56. Goskonda VR, Khan MA, Hutak CM, Reddy IK. Permeability characteristics of novel mydriatic agents using an in vitro cell culture model that utilizes SIRC rabbit corneal cells. J Pharm Sci 1999;88:180-4 (Pubitemid 29084728)
57. Goskonda VR, Hill RA, Khan MA, Reddy IK. Permeability of chemical delivery systems across rabbit corneal (SIRC) cell line and isolated corneas: a comparative study. Pharm Dev Technol 2000;5:409-16 (Pubitemid 30602849)
58. Goskonda VR, Reddy IK. Permeability of pure enantiomers of timolol across SIRC rabbit corneal cells. Pharm Pharmacol Commun 1999;5:111-15 (Pubitemid 29129424)
59. Tak RV, Pal D, Gao H, et al. Transport of acyclovir ester prodrugs through rabbit cornea and SIRC-rabbit corneal epithelial cell line. J Pharm Sci 2001;90:1505-15 (Pubitemid 32979745)
60. Talluri RS, Katragadda S, Pal D, Mitra AK. Mechanism of L-ascorbic acid uptake by rabbit corneal epithelial cells: evidence for the involvement of sodium-dependent vitamin C transporter 2. Curr Eye Res 2006;31:481-9 (Pubitemid 43884594)
61. Balakrishnan A, Jain-Vakkalagadda B, Yang C, et al. Carrier mediated uptake of L-tyrosine and its competitive inhibition by model tyrosine linked compounds in a rabbit corneal cell line (SIRC)-strategy for the design of transporter/receptor targeted prodrugs. Int J Pharm 2002;247:115-25 (Pubitemid 35341143)
62. Majumdar S, Tirucherai GS, Pal D, Mitra AK. Functional differences in nucleoside and nucleobase transporters expressed on the rabbit corneal epithelial cell line (SIRC) and isolated rabbit cornea. AAPS PharmSci 2003;5:E15
63. Al-Nakkash L, Reinach PS. Activation of a CFTR-mediated chloride current in a rabbit corneal epithelial cell line. Invest Ophthalmol Vis Sci 2001;42:2364-70 (Pubitemid 32848867)
64. Jain-Vakkalagadda B, Dey S, Pal D, Mitra AK. Identification and functional characterization of a Na+-independent neutral amino acid transporter, LAT1, in human and rabbit cornea. Invest Ophthalmol Vis Sci 2003;44:2919-27 (Pubitemid 36759753)
65. Castro-Munozledo F. Corneal epithelial cell cultures as a tool for research, drug screening and testing. Exp Eye Res 2008;86:459-69
66. Araki-Sasaki K, Ohashi Y, Sasabe T, et al. An SV40-immortalized human corneal epithelial cell line and its characterization. Invest Ophthalmol Vis Sci 1995;36:614-21
67. Offord EA, Sharif NA, Mace K, et al. Immortalized human corneal epithelial cells for ocular toxicity and inflammation studies. Invest Ophthalmol Vis Sci 1999;40:1091-101 (Pubitemid 29211446)
68. Mohan RR, Possin DE, Mohan RR, et al. Development of genetically engineered tet HPV16-E6/E7 transduced human corneal epithelial clones having tight regulation of proliferation and normal differentiation. Exp Eye Res 2003;77:395-407 (Pubitemid 37040839)
69. Huhtala A, Nurmi SK, Tahti H, et al. The immunohistochemical characterisation of an SV40-immortalised human corneal epithelial cell line. Altern Lab Anim 2003;31:409-17 (Pubitemid 37279940)
70. Sharif NA, Wiernas TK, Howe WE, et al. Human corneal epithelial cell functional responses to inflammatory agents and their antagonists. Invest Ophthalmol Vis Sci 1998;39:2562-71 (Pubitemid 28558215)
71. Carrier P, Deschambeault A, Talbot M, et al. Characterization of wound reepithelialization using a new human tissue-engineered corneal wound healing model. Invest Ophthalmol Vis Sci 2008;49:1376-85
72. Kruszewski FH, Walker TL, DiPasquale LC. Evaluation of a human corneal epithelial cell line as an in vitro model for assessing ocular irritation. Fundam Appl Toxicol 1997;36:130-40
73. Huhtala A, Alajuuma P, Burgalassi S, et al. A collaborative evaluation of the cytotoxicity of two surfactants by using the human corneal epithelial cell line and the WST-1 test. J Ocul Pharmacol Ther 2003;19:11-21 (Pubitemid 36249876)
74. Toropainen E, Ranta VP, Talvitie A, et al. Culture model of human corneal epithelium for prediction of ocular drug absorption. Invest Ophthalmol Vis Sci 2001;42:2942-8 (Pubitemid 33035294)
75. Ranta VP, Laavola M, Toropainen E, et al. Ocular pharmacokinetic modeling using corneal absorption and desorption rates from in vitro permeation experiments with cultured corneal epithelial cells. Pharm Res 2003;20:1409-16 (Pubitemid 37164049)
76. Toropainen E, Ranta VP, Vellonen KS, et al. Paracellular and passive transcellular permeability in immortalized human corneal epithelial cell culture model. Eur J Pharm Sci 2003;20:99-106 (Pubitemid 37103237)
77. Greco D, Vellonen KS, Turner HC, et al. Gene expression analysis in SV-40 immortalized human corneal epithelial cells cultured with an air-liquid interface. Mol Vis 2010;16:2109-20
78. Becker U, Ehrhardt C, Daum N, et al. Expression of ABC-transporters in human corneal tissue and the transformed cell line, HCE-T. J Ocul Pharmacol Ther 2007;23:172-81 (Pubitemid 46642159)
79. Wang S, Jiang T, Wang Z. Permeability and anticataract effects of a topical ocular drug delivery system of disulfiram. BioMedical engineering and informatics: new development and the future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics. Volume 1. BMEI; 2008. p. 596-600
80. Kimura K, Teranishi S, Nishida T. Interleukin-1beta-induced disruption of barrier function in cultured human corneal epithelial cells. Invest Ophthalmol Vis Sci 2009;50:597-603
81. Yanai R, Ko JA, Nomi N, et al. Upregulation of ZO-1 in cultured human corneal epithelial cells by a peptide (PHSRN) corresponding to the second cell-binding site of fibronectin. Invest Ophthalmol Vis Sci 2009;50:2757-64
82. Ko JA, Yanai R, Nishida T. Up-regulation of ZO-1 expression and barrier function in cultured human corneal epithelial cells by substance P. FEBS Lett 2009;583:2148-53
83. Nagai N, Inomata M, Ito Y. Contribution of aldehyde dehydrogenase 3A1 to disulfiram penetration through monolayers consisting of cultured human corneal epithelial cells. Biol Pharm Bull 2008;31:1444-8 (Pubitemid 351930666)
84. Seeber JW, Zorn-Kruppa M, Lombardi-Borgia S, et al. Characterisation of human corneal epithelial cell cultures maintained under serum-free conditions. Altern Lab Anim 2008;36:569-83
85. Wilkinson PJ, Clothier RH. Comparison of an animal product free medium and normal growth supplement on the growth and barrier integrity of a human corneal epithelial cell line. Altern Lab Anim 2005;33:509-18 (Pubitemid 41608022)
86. Reichl S. Films based on human hair keratin as substrates for cell culture and tissue engineering. Biomaterials 2009;30:6854-66
87. Karla PK, Earla R, Boddu SH, et al. Molecular expression and functional evidence of a drug efflux pump (BCRP) in human corneal epithelial cells. Cur Eye Res 2009;34:1-9
88. Jager K, Bonisch U, Risch M, et al. Detection and regulation of cationic amino acid transporters in healthy and diseased ocular surface. Invest Ophthalmol Vis Sci 2009;50:1112-21
89. Shioda R, Reinach PS, Hisatsune T, Miyamoto Y. Osmosensitive taurine transporter expression and activity in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2002;43:2916-22 (Pubitemid 34977040)
90. Jones PA, Budynsky E, Cooper KJ, et al. Comparative evaluation of five in vitro tests for assessing the eye irritation potential of hair-care products. Altern Lab Anim 2001;29:669-92 (Pubitemid 33126464)
91. Van Goethem F, Adriaens E, Alepee N, et al. Prevalidation of a new in vitro reconstituted human cornea model to assess the eye irritating potential of chemicals. Toxicol In Vitro 2006;20:1-17 (Pubitemid 41796438)
92. Cotovio J, Grandidier MH, Lelievre D, et al. In vitro assessment of eye irritancy using the Reconstructed Human Corneal Epithelial SkinEthic HCE model: application to 435 substances from consumer products industry. Toxicol In Vitro 2010;24:523-37
93. Prasanna G, Fortner J, Xiang C, et al. Ocular pharmacokinetics and hypotensive activity of PF-04475270, an EP4 prostaglandin agonist in preclinical models. Exp Eye Res 2009;89:608-17
94. Giannola LI, de Caro V, Giandalia G, et al. Ocular gelling microspheres: in vitro precorneal retention time and drug permeation through reconstituted corneal epithelium. J Ocul Pharmacol Ther 2008;24:186-96 (Pubitemid 351450479)
95. Xiang CD, Batugo M, Gale DC, et al. Characterization of human corneal epithelial cell model as a surrogate for corneal permeability assessment: metabolism and transport. Drug Metab Dispos 2009;37:992-8
96. Friend J, Kinoshita S, Thoft RA, Eliason JA. Corneal epithelial cell cultures on stromal carriers. Invest Ophthalmol Vis Sci 1982;23:41-9 (Pubitemid 12089681)
97. Chan KY, Haschke RH. Epithelial-stromal interactions: specific stimulation of corneal epithelial cell growth in vitro by a factor(s) from cultured stromal fibroblasts. Exp Eye Res 1983;36:231-46 (Pubitemid 13144996)
98. Geggel HS, Friend J, Thoft RA. Collagen gel for ocular surface. Invest Ophthalmol Vis Sci 1985;26:901-5 (Pubitemid 15063887)
99. Ohji M, SundarRaj N, Hassell JR, Thoft RA. Basement membrane synthesis by human corneal epithelial cells in vitro. Invest Ophthalmol Vis Sci 1994;35:479-85 (Pubitemid 2039174)
100. Tseng SC, Kruse FE, Merritt J, Li DQ. Comparison between serum-free and fibroblast-cocultured single-cell clonal culture systems: evidence showing that epithelial anti-apoptotic activity is present in 3T3 fibroblast-conditioned media. Curr Eye Res 1996;15:973-84 (Pubitemid 26332237)
101. Parnigotto PP, Bassani V, Montesi F, Conconi MT. Bovine corneal stroma and epithelium reconstructed in vitro: characterisation and response to surfactants. Eye 1998;12:304-10 (Pubitemid 28263876)
102. Germain L, Auger FA, Grandbois E, et al. Reconstructed human cornea produced in vitro by tissue engineering. Pathobiology 1999;67:140-7 (Pubitemid 29304375)
103. Orwin EJ, Hubel A. In vitro culture characteristics of corneal epithelial, endothelial and keratocyte cells in a native collagen matrix. Tissue Eng 2000;6:307-19 (Pubitemid 30655941)
104. Minami Y, Sugihara H, Oono S. Reconstruction of cornea in three-dimensional collagen matrix culture. Invest Ophthalmol Vis Sci 1993;34:2316-24 (Pubitemid 23191261)
105. Zieske JD, Mason VS, Wasson ME, et al. Basement membrane assembly and differentiation of cultured corneal cells: importance of culture environment and endothelial cell interaction. Exp Cell Res 1994;214:621-33 (Pubitemid 24310821)
106. Schneider AI, Maier-Reif K, Graeve T. The use of an in vitro cornea for predicting ocular toxicity. In Vitro Toxicol 1997;10:309-18
107. Schneider AI, Maier-Reif K, Graeve T. Constructing an in vitro cornea from cultures of the three specific corneal cell types. In Vitro Cell Dev Biol Anim 1999;35:515-26 (Pubitemid 29530102)
108. Carrier P, Deschambeault A, Audet C, et al. Impact of cell source on human cornea reconstructed by tissue engineering. Invest Ophthalmol Vis Sci 2009;50:2645-52
109. Larouche D, Paquet C, Fradette J, et al. Regeneration of skin and cornea by tissue engineering. Methods Mol Biol 2009;482:233-56
110. Griffith M, Osborne R, Munger R, et al. Functional human corneal equivalents constructed from cell lines. Science 1999;286:2169-72 (Pubitemid 129516294)
111. Zieske JD, Chung EH, Guo X, Hutcheon AEK. Human corneal organotypic cultures. J Toxicol Cutan Ocul Toxicol 2004;23:19-28 (Pubitemid 38352345)
112. Zorn-Kruppa M, Tykhonova S, Belge G, et al. A human corneal equivalent constructed from SV40-immortalised corneal cell lines. Altern Lab Anim 2005;33:37-45 (Pubitemid 40476881)
113. Builles N, Bechetoille N, Justin V, et al. Development of a hemicornea from human primary cell cultures for pharmacotoxicology testing. Cell Biol Toxicol 2007;23:279-92 (Pubitemid 46474918)
114. Werner A, Braun M, Reichl S, Kietzmann M. Establishing and functional testing of a canine cornea construct. Vet Ophthalmol 2008;11:280-9
115. Tegtmeyer S, Papantoniou I, Muller-Goymann CC. Reconstruction of an in vitro cornea and its use for drug permeation studies from different formulations containing pilocarpine hydrochloride. Eur J Pharm Biopharm 2001;51:119-25 (Pubitemid 32162490)
116. Tegtmeyer S, Reichl S, Muller-Goymann CC. Cultivation and characterization of a bovine in vitro model of the cornea. Pharmazie 2004;59:464-71 (Pubitemid 38828636)
117. Reichl S, Muller-Goymann CC. Development of an organotypic corneal construction as an in vitro model for permeability studies. Ophthalmologe 2001;98:853-8 (Pubitemid 32905033)
118. Reichl S, Muller-Goymann CC. The use of a porcine organotypic cornea construct for permeation studies from formulations containing befunolol hydrochloride. Int J Pharm 2003;250:191-201 (Pubitemid 35447949)
119. Bednarz J, Teifel M, Friedl P, Engelmann K. Immortalization of human corneal endothelial cells using electroporation protocol optimized for human corneal endothelial and human retinal pigment epithelial cells. Acta Ophthalmol Scand 2000;78:130-6 (Pubitemid 30201417)
120. Reichl S, Bednarz J, Muller-Goymann CC. Human corneal equivalent as cell culture model for in vitro drug permeation studies. Br J Ophthalmol 2004;88:560-5 (Pubitemid 38437881)
121. Reichl S, Dohring S, Bednarz J, Muller-Goymann CC. Human cornea construct HCC-an alternative for in vitro permeation studies? A comparison with human donor corneas. Eur J Pharm Biopharm 2005;60:305-8 (Pubitemid 40804570)
122. Meyer L, Bednarz J, Muller-Goymann CC, Reichl S. Esterase activity of human organotypic cornea construct (HCC) as in vitro model for permeation studies. Ophthalmologe 2005;102:971-80 (Pubitemid 41436901)
123. Friedrich I, Reichl S, Muller-Goymann CC. Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS). Int J Pharm 2005;305:167-75 (Pubitemid 41562227)
124. Attama A, Reichl S, Muller-Goymann CC. Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int J Pharm 2008;355:307-13
125. Attama A, Reichl S, Muller-Goymann CC. Sustained release and permeation of timolol from surface modified solid lipid nanoparticles through bio-engineered human cornea. Curr Eye Res 2009;34:698-705
126. Ali Y, Lehmussaari K. Industrial perspective in ocular drug delivery. Adv Drug Deliv Rev 2006;58:1258-68
127. Bito LZ. Species differences in the responses of the eye to irritation and trauma: a hypothesis of divergence in ocular defense mechanisms, and the choice of experimental animals for eye research. Exp Eye Res 1984;39:807-29 (Pubitemid 15199837)
128. Braun A, Hammerle S, Suda K, et al. Cell cultures as tools in biopharmacy. Eur J Pharm Sci 2000;11(Suppl 2):S51-60
129. Thiel-Demby VE, Humphreys JE, St John Williams LA, et al. Biopharmaceutics classification system: validation and learnings of an in vitro permeability assay. Mol Pharm 2009;6:11-18
130. Hahne M, Grobe G, Zorn-Kruppa M, et al. Prevalidation of a serum free human cornea construct for drug diffusion studies: development and repeatability. Pharmaceutical Sciences World Congress 2010; New Orleans
131. Liu Q, Wang Y. Development of an ex vivo method for evaluation of precorneal residence of topical ophthalmic formulations. AAPS PharmSciTech 2009;10:796-805
132. Toropainen E, Hornof M, Kaarniranta K, et al. Corneal epithelium as a platform for secretion of transgene products after transfection with liposomal gene eyedrops. J Gene Med 2007;9:208-16 (Pubitemid 46523538)
133. Hornof M, de la Fuente M, Hallikainen M, et al. Low molecular weight hyaluronan shielding of DNA/PEI polyplexes facilitates CD44 receptor mediated uptake in human corneal epithelial cells. J Gene Med 2008;10:70-80
134. de la Fuente M, Seijo B, Alonso MJ. Bioadhesive hyaluronan-chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue. Gene Ther 2008;15:668-76 (Pubitemid 351524521)
135. Puleo CM, McIntosh Ambrose W, Takezawa T, et al. Integration and application of vitrified collagen in multilayered microfluidic devices for corneal microtissue culture. Lab Chip 2009;9:3221-7
136. Zhang T, Xiang CD, Gale D, et al. Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos 2008;36:1300-7 (Pubitemid 351929314)
137. Anand BS, Mitra AK. Mechanism of corneal permeation of L-Valyl ester of acyclovir: targeting the oligopeptide transporter on the rabbit cornea. Pharm Res 2002;19:1194-202 (Pubitemid 34985004)
138. Anand BS, Nashed YE, Mitra AK. Novel dipeptide prodrugs of acyclovir for ocular herpes infections: bioreversion, antiviral activity and transport across rabbit cornea. Cur Eye Res 2003;26:151-63 (Pubitemid 36829642)
139. Gunda S, Hariharan S, Mitra AK. Corneal absorption and anterior chamber pharmacokinetics of dipeptide monoester prodrugs of ganciclovir (GCV): in vivo comparative evaluation of these prodrugs with Val-GCV and GCV in rabbits. J Ocul Pharmacol Ther 2006;22:465-76 (Pubitemid 46110643)
140. Jain-Vakkalagadda B, Pal D, Gunda S, et al. Identification of a Na+-dependent cationic and neutral amino acid transporter, B(0,+), in human and rabbit cornea. Mol Pharm 2004;1:338-46
141. Kraft ME, Glaeser H, Mandery K, et al. The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol Vis Sci 2010;51:2504-11
142. Senthilkumari S, Velpandian T, Biswas NR, et al. Evaluation of the modulation of P-Glycoprotein (P-gp) on the intraocular disposition of its substrates in rabbits. Cur Eye Res 2008;33:333-43 (Pubitemid 351507755)
143. Maxey KM, Johnson JL, LaBrecque J. The hydrolysis of bimatoprost in corneal tissue generates a potent prostanoid FP receptor agonist. Surv Ophthalmol 2002;47:S34-40 (Pubitemid 35232217)
144. Mastyugin V, Aversa E, Bonazzi A, et al. Hypoxia-induced production of 12-hydroxyeicosanoids in the corneal epithelium: involvement of a cytochrome P-4504B1 isoform. J Pharmacol Exp Ther 1999;289:1611-19 (Pubitemid 29246697)
145. Stoltz RA, Conners MS, Dunn MW, Schwartzman ML. Effect of metabolic inhibitors on arachidonic acid metabolism in the corneal epithelium: evidence for cytochrome P450-mediated reactions. J Ocul Pharmacol 1994;10:307-17 (Pubitemid 24119452)
146. Stoilov I, Akarsu N, Alozie I, et al. Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1. Am J Hum Genet 1998;62:573-84 (Pubitemid 28164614)
147. Lee VHL. Esterase activities in adult rabbit eyes. J Pharm Sci 1983;72:239-44
148. Anand BS, Katragadda S, Nashed YE, Mitra AK. Amino acid prodrugs of acyclovir as possible antiviral agents against ocular HSV-1 infections: interactions with the neutral and cationic amino acid transporter on the corneal epithelium. Curr Eye Res 2004;29:153-66 (Pubitemid 39556924)
149. Bertelmann E, Knapp S, Rieck P, et al. Transcorneal-paracorneal penetration route for topical application of drugs to the eye. Mycophenolate mofetil as model substance. Ophthalmologe 2003;100:696-701 (Pubitemid 37158583)
150. Lee VHL, Chang SC, Oshiro CM, Smith RE. Ocular esterase composition in albino and pigmented rabbits: possible implications in ocular prodrug design and evaluation. Curr Eye Res 1985;4:1117-25 (Pubitemid 16254493)
151. Schoenwald RD, Zhu J. The ocular pharmacokinetics of ketanserin and its metabolite, ketanserinol, in albino rabbits. J Ocul Pharmacol Ther 2000;16:481-95
152. Singh SV, Hong TD, Srivastava SK, Awasthi YC. Characterization of glutathione S-transferases of human cornea. Exp Eye Res 1985;40:431-7 (Pubitemid 16153375)
153. Watkins JB, Wirthwein DP, Sanders RA. Comparative study of Phase II biotransformation in rabbit ocular tissues. Drug Metab Dispos 1991;19:708-13
154. Campbell DA, Schoenwald RD, Duffel MW, Barfknecht CF. Characterization of arylamine acetyltransferase in the rabbit eye. Invest Ophthalmol Vis Sci 1991;32:2190-200