Enhancement of ocular drug penetration

Critical Reviews in Therapeutic Drug Carrier Systems

Volumn 16, Issue 1, 1999, Pages 85-146

  Sasaki, Hitoshi ^a   Yamamura, Kenzo ^b   Mukai, Takahiro ^b   Nishida, Koyo ^b   Nakamura, Junzo ^b   Nakashima, Mikiro ^a   Ichikawa, Masataka ^a  

^a NAGASAKI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b NAGASAKI UNIVERSITY   (Japan)

Author keywords

Barrier; Drug delivery system; Enhancer; Eye; Ion pair; Iontophoresis; Ocular penetration; Pharmacokinetics; Prodrug; Promoter

Indexed keywords

ACICLOVIR; ADRENALIN; ADRENALONE; AGENTS ACTING ON THE EYE; ALPRENOLOL; ATENOLOL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BETAXOLOL; BILE SALT; CARBONATE DEHYDRATASE INHIBITOR; CARNOSINE; DEXAMETHASONE; FLUOROURACIL; GENTAMICIN; NADOLOL; PHENYLEPHRINE; PILOCARPINE; PINDOLOL; PREDNISOLONE; PROPRANOLOL; PROSTAGLANDIN F2 ALPHA; SALICYLIC ACID DERIVATIVE; STEROID; SURFACTANT; TERBUTALINE; TILISOLOL; TIMOLOL; TOBRAMYCIN; UNINDEXED DRUG; VANCOMYCIN;

ANTERIOR EYE CHAMBER; AQUEOUS HUMOR FLOW; CARDIOVASCULAR EFFECT; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG PENETRATION; ECHOOCULOGRAPHY; EYE DISEASE; EYE IRRITATION; GLAUCOMA; HEADACHE; HUMAN; ION PAIR EXTRACTION; IONTOPHORESIS; LIPOPHILICITY; MEMBRANE PERMEABILITY; MIOSIS; NONHUMAN; REVIEW; TOPICAL DRUG ADMINISTRATION;

EID: 0032941568     PISSN: 07434863     EISSN: None     Source Type: Journal    
DOI: 10.1615/critrevtherdrugcarriersyst.v16.i1.20     Document Type: Review

References (198)

1. Raviola, G., The structural basis of the blood-ocular barriers, Exp. Eye Res., 25, 27, 1977.
2. Stjernschantz, J. and Astin, M., Anatomy and physiology of the eye. Physiological aspects of ocular drug therapy, in Biopharmaceutics of Ocular Drug Delivery, Edman, P., Ed., Boca Raton, FL: CRC Press, 1993, 1.
3. Lee, V. H. L. and Robinson, J. R., Topical ocular drug delivery: Recent developments and future challenges, J. Ocul Pharmacol., 2, 67, 1986.
4. Schoenwald, R. D., Ocular drug delivery. Pharmacokinetic considerations, Clin. Pharmacokinet., 18, 255, 1990.
5. Doane, M. G., Jensen, A. D., and Dohlman, C. H., Penetration routes of topically applied eye medications, Am. J. Ophthalmol., 85, 383, 1978.
6. Sasaki, H., Ichikawa, M., Kawakami, S., Yamamura, K., Nishida, K., and Nakamura, J., In situ ocular absorption of tilisolol through ocular membranes in albino rabbits, J. Pharm. Sci., 85, 940, 1996.
7. Sasaki, H., Ichikawa, M., Kawakami, S., Yamamura, K., Mukai, T., Nishida, K., and Nakamura, J., In situ ocular absorption of ophthalmic β-blockers through ocular membranes in albino rabbits, J. Pharm. Pharmacol., 49, 140, 1997.
8. Sasaki, H., Yamamura, K., Nishida, K., Nakamura J., and Ichikawa, M., Delivery of drugs to the eye by topical application, Prog. Ret. Eye Res., 15, 583, 1996.
9. Mishima, S., Gasset, A., Klyce, S. D. J., and Baum, J. L., Determination of tear volume and tear flow, Invest. Ophthalmol., 5, 264, 1966.
10. Sørensen, T. and Jensen, F. T., Tear flow in normal human eyes: Determination by means of radioisotope and γ camera, Acta Ophthalmol., 57, 564, 1979.
11. Patton, T. F. and Robinson, J. R., Quantitative precorneal disposition of topically applied pilocarpine nitrate in rabbit eyes, J. Pharm. Sci., 65, 1295, 1976.
12. Chrai, S. S., Patton, T. F., Mehta, A., and Robinson, J. R., Lacrimal and instilled fluid dynamics in rabbit eyes, J. Pharm. Sci., 62, 1112, 1973.
13. Zimmerman, T. J., Sharir, M., Nardin, G. F., and Fuqua, M., Therapeutic index of epinephrine and dipivefrin with nasolacrimal occlusion, Am. J. Ophthalmol., 114, 8, 1992.
14. Norn, M., The effects of drugs on tear flow, Trans. Ophthalmol. Soc. UK, 104, 410, 1985.
15. Mikkelson, T. J., Chrai, S. S., and Robinson, J. R., Altered bioavailability of drugs in the eye due to drug-protein interaction, J. Pharm. Sci., 62, 1948, 1973.
16. Reinsten, D. Z., Silverman, R. H., Rondeau, M. J., and Coleman, D. J., Epithelial and corneal thickness measurements by high-frequency ultrasound digital signal processing, Ophthalmology, 101, 140, 1994.
17. Huang, H.-S., Schoenwald, R. D., and Lach, J. L., Corneal penetration behavior of β-blocking agents, II. Assessment of barrier contributions, J. Pharm. Sci., 72, 1272, 1983.
18. Sasaki, H., Igarashi, Y., Nagano, T., Yamamura, K., Nishida, K., and Nakamura, J., Penetration of β-blockers through ocular membranes in albino rabbits, J. Pharm. Pharmacol., 47, 17, 1995.
19. Watsky, M. A., Jablonski, M., and Edelhauser, H. F., Comparison of conjunctival and corneal surface areas in rabbit and human, Curr. Eye Res., 7, 483, 1988.
20. Huang, A. J. W., Tseng, S. C. G., and Kenyon, K. R., Paracellular permeability of corneal and conjunctival epithelia, Invest. Ophthalmol. Vis. Sci., 30, 684, 1989.
21. Hamalainen, K. M., Kananen, K., Auriola, S., Kontturi, K., and Urtti, A., Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera, Invest. Ophthalmol. Vis. Sci., 38, 627, 1997.
22. +-dependent L-arginine transport in the pigmented rabbit conjunctiva, Exp. Eye Res., 65, 547, 1997.
23. Luo, A. M., Sasaki, H., and Lee, V. H. L., Ocular drug interactions involving topically applied timolol in the pigmented rabbit, Curr. Eye Res., 10, 231, 1991.
24. Ahmed, I. and Patton, T. F., Disposition of timolol and inulin in the rabbit eye following corneal versus non-corneal absorption, Int. J. Pharm., 38, 9, 1987.
25. Jones, R. F. and Maurice, D. M., New methods of measuring the rate of aqueous flow in man with fluorescein, Exp. Eye Res., 5, 208, 1966.
26. Zane, P. A., Brindle, S. D., Gause, D. O., O'Buck, A. J., Raghavan, P. R., and Tripp, S. L., Physicochemcial factors associated with binding and retention of compounds in ocular melanin of rats: Correlations using data from whole-body autoradiography and molecular modeling for multiple linear regression analyses, Pharm. Res., 7, 935, 1990.
27. Ahmed, I., Francoeur, M. L., Thombre, A. G., and Patton, T. F., The kinetics of timolol in the rabbit lens: Implications for ocular drug delivery, Pharm. Res., 6, 772, 1989.
28. Smith, T. J., Pearson, P. A., Blandford, D. L., Brown, J. D., Goins, K. A., Hollins, J. L., Schmeisser, E. E., Glavinos, P., Baldwin, L. B., and Ashton, P., Intravitreal sustained-release gancyclovir, Arch. Ophthalmol., 110, 255, 1992.
29. Ohtori, A. and Tojo, K., In vivo/in vitro correlation of intravitreal delivery of drugs with the help of computer simulation, Biol. Pharm. Bull., 17, 283, 1994.
30. Lee, V. H. L. and Robinson, J. R., Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits, J. Pharm. Sci., 68, 673, 1979.
31. Himmelstein, K. J., Guvenir, I., and Patton, T. F., Preliminary pharmacokinetic model of pilocarpine uptake and distribution in the eye, J. Pharm. Sci., 67, 603, 1978.
32. Makoid, M. C. and Robinson, J. R., Pharmacokinetics of topically applied pilocarpine in the albino rabbit eye, J. Pharm. Sci., 68, 435, 1979.
33. Miller, S. C., Himmelstein, K. J., and Patton, T. F., A physiologically based pharmacokinetic model for the intraocular distribution of pilocarpine in rabbits, J. Pharmacokinet. Biopharm., 9, 653, 1981.
34. Sieg, J. W. and Robinson, J. R., Mechanistic studies on transcorneal permeation of fluorometholone, J. Pharm. Sci., 70, 1026, 1981.
35. 3H hydrochloride, J. Pharmacokinet. Biopharm., 14, 175, 1986.
36. Eller, M. G., Schoenwald, R. D., Dixson, J. A., Segarra, T., and Barfknecht, C. F., Topical carbonic anhydrase inhibitors IV: Relationship between excised corneal permeability and pharmacokinetic factors, J. Pharm. Sci., 74, 525, 1985.
37. Grass, G. M. and Lee, V. H. L., A model to predict aqueous humor and plasma pharmacokinetics of ocularly applied drugs, Invest. Ophthalmol. Vis. Sci., 34, 2251, 1993.
38. Finne, U. and Urtti, A., Pharmacokinetic simulation reveals in vivo deviations from in vitro release of timolol from polymer matrices, Int. J. Pharm., 84, 217, 1992.
39. Sugaya, M. and Nagataki, S., Kinetics of topical pilocarpine in the human eye, Jpn. J. Ophthalmol., 22, 127, 1978.
40. Röjanasakul, Y., Wang, L.-Y., Bhat, M., Glover, D. D., Malanga, C. J., and Ma, J. K. H., The transport barrier of epithelia: A comparative study on membrane permeability and charge selectivity in the rabbit, Pharm. Res., 9, 1029, 1992.
41. Klyce, S. D. and Crosson, C. E., Transport processes across the rabbit corneal epithelium: A review, Curr. Eye Res., 4, 323, 1985.
42. Schoenwald, R. D. and Ward, R. L., Relationship between steroid permeability across excised rabbit cornea and octanol-water partition coefficients, J. Pharm. Sci., 67, 786, 1978.
43. Grass, G. M. and Robinson, J. R., Mechanisms of corneal drug penetration. I: In vivo and in vitro kinetics, J. Pharm. Sci., 77, 3, 1988.
44. Chien, D.-S., Sasaki, H., Bundgaard, H., Buur, A., and Lee, V. H. L., Role of enzymatic lability in the corneal and conjunctival penetration of timolol ester prodrugs in the pigmented rabbit, Pharm. Res., 8, 728, 1991.
45. Wang, W., Sasaki, H., Chien, D.-S., and Lee, V. H. L., Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: A comparison with corneal penetration, Curr. Eye Res., 6, 571, 1991.
46. Mitra, A. K. and Mikkelson, T. J., Mechanism of transcorneal permeation of pilocarpine, J. Pharm. Sci., 77, 771, 1988.
47. Ashton, P., Podder, S.K., and Lee, V.H.L., Formulation influence on conjunctival penetration of four ß-blockers in the pigmented rabbit: A comparison with corneal penetration, Pharm. Res., 8, 1166, 1991.
48. Kyyrönen, K. and Urtti, A., Effects of epinephrine and solution pH on ocular and systemic absorption of ocularly applied timolol in rabbits, J. Pharm. Sci., 79, 688, 1990.
49. Röjanasakul, Y. and Robinson, J. R., Transport mechanisms of the cornea: Characterization of barrier permselectivity, Int. J. Pharm., 55, 237, 1989.
50. Liaw, J., Röjanasakul, Y., and Robinson, J. L., The effect of drug charge type and charge density on corneal transport, Int. J. Pharm., 88, 111, 1992.
51. Eller, M. G., Schoenwald, R. D., Dixson, J. A., Segarra, T., and Barfknecht, C. F., Topical carbonic anhydrase inhibitors, III. Optimization model for corneal penetration of ethoxzolamide analogues, J. Pharm. Sci., 74, 155, 1985.
52. Cooperstein, D. F., Amino acid transport by corneal epithelial cells from the toad, bufomarinus, Comp. Biochem. Facial., 81, 427, 1985.
53. Lee, V. H. L., Esterase activities in adult rabbit eyes, J. Pharm. Sci., 72, 239, 1983.
54. Lee, V. H. L., Chien, D.-S., and Sasaki, H., Ocular ketone reductase distribution and its role in the metabolism of ocularly applied levobunolol in the pigmented rabbit, J. Pharmacol. Exp. Ther., 246, 871, 1988.
55. Lee, V. H. L., Carson, L. W., Dodda Kashi, S., and Stratford, R. E., Metabolic and permeation barriers to the ocular absorption of topically applied enkephalins in albino rabbits, J. Ocul. Pharmacol., 2, 345, 1986.
56. Bodor, N., El-Koussi, A., Kano, M., and Nakamura, T., Improved delivery through biological membranes, 26. Design, synthesis, and pharmacological activity of a novel chemical delivery system for β-adrenergic blocking agents, J. Med. Chem., 31, 100, 1988.
57. El-Koussi, A. A. and Bodor, N., Formation of propranolol in the iris-ciliary body from its propranolol ketoxime precursor - a potential antiglaucoma drug, Int. J. Pharm., 53, 189, 1989.
58. Bodor, N. and Prokai, L., Site-and stereo-specific ocular drug delivery by sequential enzymatic bioactivation, Pharm. Res., 7, 723, 1990.
59. Bodor, N., Retrometabolic drug design concepts in ophthalmic target-specific drug delivery, Adv. Drug Del. Rev., 16, 21, 1995.
60. Bundgaard, H., Buur, A., Chang, S.-C., and Lee, V. H. L., Timolol prodrugs: Synthesis, stability and lipophilicity of various alkyl, cycloalkyl and aromatic esters of timolol, Int. J. Pharm., 46, 77, 1988.
61. Mandel, A., Stentz, F., and Kitabchi, A. E., Dipivalyl epinephrine: A new prodrug in the treatment of glaucoma, Ophthalmology, 85, 268, 1978.
62. Lee, V. H. L. and Li, V. H. L., Prodrugs for improved ocular drug delivery, Adv. Drug Del. Rev., 3, 1, 1989.
63. Järvinen, T. and Järvinen, K., Prodrugs for improved ocular drug delivery, Adv. Drug Del. Rev., 19, 203, 1996.
64. Leibowitz, H. M., Kupferman, A., Stewart, R. H., and Kimbrough, R. L., Evaluation of dexamethasone acetate as a topical ophthalmic formulation, Am. J. Ophthalmol., 86, 418, 1978.
65. Leibowitz, H. M. and Kupferman, A., Anti-inflammatory effectiveness in the cornea of topically administered prednisolone, Invest. Ophthalmol., 13, 757, 1974.
66. Wei, C., Anderson, J. A., and Leopold, I., Ocular absorption and metabolism of topically applied epinephrine and a dipivalyl ester of epinephrine, Invest. Ophthalmol. Vis. Sci., 17, 315, 1978.
67. Redell, M. A., Yang, D. C., and Lee, V. H. L., The role of esterase activity in the ocular disposition of dipivalyl epinephrine in rabbits, Int. J. Pharm., 17, 299, 1983.
68. Anderson, J. A., Systemic absorption of topical ocularly applied epinephrine and dipivefrin, Arch. Ophthalmol., 98, 350, 1980.
69. Kohn, A. N., Moss, A. P., Hargett, N. A., Ritch, R., Smith, H., and Podos, S. M., Clinical comparison of dipivalyl epinephrine and epinephrine in the treatment of glaucoma, Am. J. Ophthalmol., 87, 196, 1979.
70. Novack, G. D., Ophthalmic β-blockers since timolol, Surv. Ophthalmol., 31, 307, 1987.
71. Van Buskirk, E. M., Adverse reactions from timolol administration, Ophthalmology, 87, 447, 1980.
72. Duzman, E., Chen, C.-C., Anderson, J., Blumenthal, M., and Twizer, H., Diacetyl derivative of nadolol: Ocular pharmacology and short-term ocular hypotensive effect in glaucomatous eyes, Arch. Ophthalmol., 100, 1916, 1982.
73. Chang, S.-C., Bundgaard, H., Buur, A., and Lee, V. H. L., Low dose O-butyryl timolol improves the therapeutic index of timolol in the pigmented rabbit, Invest. Ophthalmol. Vis. Sci., 29, 626, 1988.
74. Alexander, J., Cargill, R., Michelson, S. R., and Schwam, H., (Acyloxy)alkyl carbamates as novel bioreversible prodrugs for amines: Increased permeation through biological membranes, J. Med. Chem., 31, 318, 1988.
75. Phipps, T. L., Potter, D. E., and Rowland, J. M., Effects of ibuterol, a β-2 adrenergic prodrug, on intraocular pressure, J. Ocul. Pharmacol., 3, 225, 1986.
76. Sasaki, H., Igarashi, Y., Nishida, K., and Nakamura, J., Ocular delivery of the β-blocker, tilisolol, through the prodrug approach, Int. J. Pharm., 93, 49, 1993.
77. Chang, S.-C., Bundgaard, H., Buur, A., and Lee, V. H. L., Improved corneal penetration of timolol by prodrugs as a means to reduce systemic drug load, Invest. Ophthalmol. Vis. Sci., 28, 487, 1987.
78. Bundgaard, H., Buur, A., Chang, S.-C., and Lee, V. H. L., Prodrugs of timolol for improved ocular delivery: Synthesis, hydrolysis kinetics and lipophilicity of various timolol esters, Int. J. Pharm., 33, 15, 1986.
79. Buur, A., Bundgaard, H., and Lee, V. H. L., Prodrugs of propranolol: Hydrolysis and intramolecular aminolysis of various propranolol esters and an oxazolidin-2-one derivative, Int. J. Pharm., 42, 51, 1988.
80. Pech, B., Chetoni, P., Saettone, M. F., Duval, D., and Benoit, J.-P., Preliminary evaluation of a series of amphiphilic timolol prodrugs: Possible evidence for transscleral absorption, J. Ocul. Pharmacol., 9, 141, 1993.
81. Pech, B. P., Proust, J.-E., Bouligand, Y., and Benoit, J.-P., Tensioactivity and supramolecular organization of the palmitoyl prodrug of timolol, Pharm. Res., 14, 37, 1997.
82. Quigley, H. A., Pollack, I. P., and Harbin, T. S. J., Pilocarpine ocuserts. Long-term clinical trials and selected pharmacodynamics, Arch. Ophthalmol., 93, 771, 1975.
83. Macoul, K. L. and Pavan-Langston, D., Pilocarpine ocusert system for sustained control of ocular hypertension, Arch. Ophthalmol., 93, 587, 1975.
84. Bundgaard, H., Falch, E., Larsen, C., Mosher, G. L., and Mikkelson, T. J., Pilocarpic acid esters as novel sequentially labile pilocarpine prodrugs for improved ocular delivery, J. Med. Chem., 28, 979, 1985.
85. Bundgaard, H., Falch, E., Larsen, C., and Mikkelson, T.J., Pilocarpine prodrugs I. Synthesis, physicochemical properties and kinetics of lactonization of pilocarpic acid esters, J. Pharm. Sci., 75, 36, 1986.
86. Bundgaard, H., Falch, E., Larsen, C., Mosher, G. L., and Mikkelson, T.J., Pilocarpine prodrugs, II. Synthesis, stability, bioconversion, and physicochemical properties of sequentially labile pilocarpine acid diesters, J. Pharm. Sci., 75, 775, 1986.
87. Järvinen, T., Suhonen, P., Auriola, S., Vepsäläinen, J., Urtti, A., and Peura, P., O,O′-(1,4-Xylylene)bispilocarpic acid esters as new potential double prodrugs of pilocarpine for improved ocular delivery. I. Synthesis and analysis, Int. J. Pharm., 75, 249, 1991.
88. Järvinen,T., Suhonen, P., Urtti, A., and Peura, P., O,O′-(1,4-Xylylene)bispilocarpic acid esters as new potential double prodrugs of pilocarpine for improved ocular delivery, II. Physicochemical properties, stability, solubility and enzymatic hydrolysis, Int. J. Pharm., 75, 259, 1991.
89. Suhonen, P., Järvinen, T., Rytkonen, P., Peura, P., and Urtti, A., Improved corneal pilocarpine permeability with O,O′-(1,4-xylylene) bispilocarpic acid ester double prodrugs, Pharm. Res., 8, 1539, 1991.
90. Suhonen, P., Järvinen, T., Lehmussaari, K., Reunamäki, T., and Urtti, A., Ocular absorption and irritation of pilocarpine prodrug is modified with buffer, polymer, and cyclodextrin in the eye drop, Pharm. Res., 12, 529, 1995.
91. Yuan, S.-S. and Bodor, N., Synthesis and activity of (R)-(-)-m-trimethylacetoxy-α-[(methylamino)methyl]benzylalcohol hydrochloride: A prodrug form of (R)-(-)-phenylephrine, J. Pharm. Sci., 65, 929, 1976.
92. Schoenwald, R. D., Folk, J. C., Kumar, V., and Piper, J. G., In vivo comparison of phenylephrine and phenylephrine oxazolidine instilled in the monkey eye, J. Ocul. Pharmacol., 3, 333, 1987.
93. Chien, D.-S. and Schoenwald, R. D., Ocular pharmacokinetics and pharmacodynamics of phenylephrine and phenylephrine oxazolidine in rabbit eyes, Pharm. Res., 7, 476, 1990.
94. Green, H. and Leopold, I. H., Effects of locally administered Diamox, Am. J. Ophthalmol., 40, 137, 1955.
95. Woltersdorf, Jr, O. W., Schwam, H., Bicking, J. B., Brown, S. L., deSolms, S. J., Fishman, D. R., Graham, S. L., Gautheron, P. D., Hoffman, J. M., Larson, R. D., Lee, W. S., Michelson, S. R., Robb, C. M., Share, N. N., Shepard, K. L., Smith, A. M., Smith, R. L., Sondey, J. M., Strohmaier, K. M., Sugrue, M. F., and Viader, M. P., Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide, J. Med. Chem., 32, 2486, 1989.
96. Larsen, J. D., Bundgaard, H., and Lee, V. H. L., Prodrug forms for the sulfonamide group, II. Water-soluble amino acid derivatives of N-methylsulfonamides as possible prodrugs, Int. J. Pharm., 47, 103, 1988.
97. Bodor, N. and Elkoussi, A., Improved delivery through biological membranes. LVI. Pharmacological evaluation of alprenoxime - a new potential antiglaucoma agent, Pharm. Res., 8, 1389, 1991.
98. Prokai, L., Wu, W.-M., Somogyi, G., and Bodor, N., Ocular delivery of the β-adrenergic antagonist alprenolol by sequential bioactivation of its methoxime analogue, J. Med. Chem., 38, 2018, 1995.
99. Bodor, N., Kaminski, J. J., and Roller, R. G., Improved delivery through biological membranes, VI. Potent sympathomimetic adrenalone derivatives, Int. J. Pharm., 1, 189, 1978.
100. Bodor, N. and Visor, G., Formation of adrenaline in the iris-ciliary body from adrenalone diesters, Exp. Eye Res., 38, 621, 1984.
101. Bodor, N. and Visor, G., Improved delivery through biological membranes, XVII. A sitespecific chemical delivery system as a short-acting mydriatic agent, Pharm. Res., 4, 168, 1984.
102. Bito, L. Z., Prostaglandins: A new approach to glaucoma management with a new, intriguing side effect, Surv. Ophthalmol., 41, S1, 1997.
103. 2α, Brit. J. Ophthalmol., 78, 560, 1994.
104. Resul, B., Stjernschantz, J., Selen, G., and Bito, L., Structure-activity relationships and receptor profiles of some ocular hypotensive prostanoids, Surv. Ophthalmol., 41, S47, 1997.
105. 2α analog, on aqueous humor dynamics in human eyes, Ophthalmology, 100, 1297, 1993.
106. 2α prodrugs in rabbit cornea and conjunctiva, J. Pharm. Sci., 86, 1180, 1997.
107. Maudgal, P. C., Clereq, K. D., Descamps, J., and Missotten, L., Topical treatment of experimental herpes simplex keratouveitis with 2′-O-glycylacyclovir, Arch. Ophthalmol., 102, 140, 1984.
108. Hughes, P. M. and Mitra, A. K., Effect of acylation on the ocular disposition of acyclovir. II. Corneal permeability and anti-HSV 1 activity of 2′-esters in rabbit epithelial keratitis, J. Ocul. Pharmacol., 9, 299, 1993.
109. Narurkar, M. M. and Mitra, A. K., Prodrugs of 5-iodo-2′-deoxyuridine for enhanced ocular transport, Pharm. Res., 6, 887, 1989.
110. Chanalet, L. and Lapalus, P., Drugs designed to maintain the transparence of the ocular lens, Fundam. Clin. Pharmacol., 8, 322, 1994.
111. Chanalet, L., Ettaiche, M., Baudouin, C., and Lapalus, P., Distribution of salicylate in pigmented rabbit ocular tissues after application of a prodrug, sodium monomethyl trisilanol orthohydroxybenzoate: In vivo and ex vivo studies, J. Ocul. Pharmacol. Ther., 11, 83, 1995.
112. Babizhayev, M. A., Yermakova, V. N., Sakina, N. L., Evstigneeva, R. P., Rozhkova, E. A., and Zheltukhina, G. A., N-α-Acetylcarnosine in a prodrug of L-carnosine in ophthalmic application as antioxidant, Clin. Chim. Acta, 254, 1, 1996.
113. Wang, W., Bundgaard, H., Buur, A., and Lee, V. H. L., Corneal penetration of 5-fluorouracil and its improvement by prodrug derivatization in the albino rabbit: Implication in glaucoma filtration surgery, Curr. Eye Res., 10, 87, 1991.
114. Chetoni, P., Crotti, P., and Saettone, M. F., Albuterol prodrugs for ocular administration: Synthesis and evaluation of the physicochemical and IOP-depressant properties of three albuterol triesters, Int. J. Pharm., 105, 147, 1994.
115. Neubert, R., Ion pair transport across membranes, Pharm. Res., 6, 743, 1989.
116. Wilson, C. G., Tomlinson, E., Davis, S. S., and Olejnik, O., Altered ocular absorption and disposition of sodium cromoglycate upon ion-pair and complex coacervate formation with dodecylbenzyldimethylammonium chloride, J. Pharm. Pharmacol., 31, 749, 1981.
117. Ahmed, M., Hadgraft, J., and Kellaway, I. W., The effect of bile salts on the interfacial transport of phenothiazines, Int. J. Pharm., 12, 219, 1982.
118. Hadgraft, J., Walters, K. A., and Wotton, P. K., Facilitated transport of sodium salicylate across an artificial lipid membrane by Azone, J. Pharm. Pharmacol., 37, 725, 1985.
119. Kato, A. and Iwata, S., In vitro study on corneal permeability to bunazosin, J. Pharmacobio-Dyn., 11, 115, 1988.
120. Kato, A. and Iwata, S., Studies on improved corneal permeability to bunazosin, J. Pharmacobio-Dyn., 11, 330, 1988.
121. Lichtenberg, D., Characterization of the solubilization of lipid bilayers by surfactants, Biochim. Biophys. Acta, 821, 470, 1985.
122. Nishihata, T., Miyake, M., and Kamada, A., Study on the mechanism behind adjuvant action of diethylethoxymethylene malonate enhancing the rectal absorption of cefmetazole and lysozyme, J. Pharmacobio-Dyn., 7, 607, 1984.
123. Harris, D., Liaw, J.-H., and Robinson, J. R., Ocular delivery of peptide and protein drugs, Adv. Drug Del. Rev., 8, 331, 1992.
124. Gumbiner, B., Structure, biochemistry, and assembly of epithelial tight junctions, Am. J. Physiol., 253, C749, 1987.
125. Anderson, J. M. and Van Itallie, C. M., Tight junctions and the molecular basis for regulation of paracellular permeability, Am. J. Physiol., 269, G467, 1995.
126. Takeichi, M., Cadherin cell adhesion receptors as a morphogenetic regulator, Science, 251, 1451, 1991.
127. Buxton, R. S., Cowin, P., Franke, W. W., Garrod, D. R., Green, K. J., King, I. A., Koch, P. J., Magee, A. I., Rees, D. A., Stanley, J. R., and Steinberg, M. S., Nomenclature of the desmosomal cadherins, J. Cell Biol., 121, 481, 1993.
128. Beyer, E. C., Gap junctions, Int. Rev. Cytol., 137, 1, 1993.
129. Tønjum, A. M., Permeability of horseradish peroxidase in the rabbit corneal epithelium, Acta Ophtalmol., 52, 650, 1974.
130. Stevenson, B. R., Siliciano, J. D., Mooseker, M. S., and Goodenough, D. A., Identification of ZO-1: A high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia, J. Cell Biol., 103, 755, 1986.
131. Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A.,Yonemura, S., Tsukita, S., and Tsukita, S., Occludin: A novel integral membrane protein localizing at tight junctions, J. Cell Biol., 123, 1777, 1993.
132. Craig, W. S. and Prado, J. V., α-Actinin localization in the junction complex of the intestinal epithelial cells, J. Cell Biol., 80, 203, 1979.
133. Hochman, J. and Artursson, P., Mechanisms of absorption enhancement and tight junction regulation, J. Contr. Rel., 29, 253, 1994.
134. Rojanasakul, Y. and Robinson, J. R., The cytoskeleton of the cornea and its role in tight junction permeability, Int. J. Pharm., 68, 135, 1991.
135. Hosoya, K. and Lee, V. H. L., Cidofovir transport in the pigmented rabbit conjunctiva, Curr. Eye Res., 16, 693, 1997.
136. Hochman, J. H., Fix J. A., and LeCluyse, E. L., In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcarnitine, J. Pharmacol. Exp. Ther., 269, 813, 1994.
137. Anderberg, E. K. and Artursson, P., Epithelial transport of drugs in cell culture, VIII. Effects of sodium dodecyl sulfate on cell membrane and tightjunction permeability in human intestinal epithelial (Caco-2) cells, J. Pharm. Sci., 82, 392, 1993.
138. Madara, J. L. and Pappenheimer, J. R., Structural basis for physiological regulation of paracellular pathways in intestinal epithelia, J. Membr. Biol., 100, 149, 1987.
139. Martinez-Palomo, A. and Erlij, D., Structure of tight junctions in epithelia with different permeability, Proc. Nat. Acad. Sci. USA, 72, 4487, 1975.
140. Anzai, K., Utsumi, H., Inoue, K., Nojima, S., and Kwan, T., Electron spin resonance studies on the interaction between liposomal membrane and Triton X-100, Chem. Pharm. Bull., 28, 1762, 1980.
141. Inoue, K. and Kitagawa, T., Effect of lipid composition on sensitivity of lipid membranes to Triton X-100, Biochim. Biophys. Acta, 426, 1, 1976.
142. Marsh, R. J. and Maurice, D. M., The influence of non-ionic detergents and other surfactants on human corneal permeability, Exp. Eye Res., 11, 43, 1971.
143. Saettone, M. F., Chetoni, P., Cerbai, R., Mazzanti, G., and Braghiroli, L., Evaluation of ocular permeation enhancers: In vitro effects on corneal transport of four β-blockers, and in vitro/in vivo toxic activity, Int. J. Pharm., 142, 103, 1996.
144. Carey, M. C. and Small, D. M., Micelle formation by bile salts, Arch. Int. Med., 130, 506, 1972.
145. Small, D. M., The formation of gallstones, Adv. Int. Med., 16, 243, 1970.
146. O'Connor, C. J., Wallace, R. G., Iwamoto, K., Taguchi, T., and Sunamoto, J., Bile salt damage of egg phosphatidylcholine liposomes, Biochim. Biophys. Acta, 817, 95, 1985.
147. Fasano, A., Budillon, G., Guandalini, S., Cuomo, R., Parrilli, G., Cangiotti, A. M., Morroni, M., and Rubino, A., Bile acids reversible effects on small intestinal permeability. An in vitro study in the rabbit, Dig. Dis. Sci., 35, 801, 1990.
148. Morimoto, K., Nakai, T., and Morisaka, K., Evaluation of permeability enhancement of hydrophilic compounds and macromolecular compounds by bile salts through rabbit corneas in vitro, J. Pharm. Pharmacol., 39, 124, 1987.
149. Longenecker, J. P., Moses, A. C., Flier, J. S., Silver, R. D., Carey, M. C., and Duvovi, E. J., Effects of sodium taurodihydrofusidate on nasal absorption of insulin in sheep, J. Pharm. Sci., 76, 351, 1987.
150. Gullikson, G. W., Cline, W. S., Lorenzsonn, V., Benz, L., Olsen, W. A., and Bass, P., Effects of anionic surfactants on hamster small intestinal membrane structure and function: Relationship to surface activity, Gastroenterology, 73, 501, 1977.
151. Golden, G. M., McKie, J. E., and Potts, R. O., Role of SC lipid fluidity in transdermal drug flux, J. Pharm. Sci., 76, 25, 1987.
152. Muranishi, S., Absorption enhancers, Crit. Rev. Ther. Drug Carrier Syst., 7, 1, 1990.
153. Hayashi, M., Tomita, M., and Awazu, S., Transcellular and paracellular contribution to transport processes in the colorectal route, Adv. Drug Del. Rev., 28, 191, 1997.
154. Tomita, M., Hayashi, M., Horie, T., Ishizawa, T., and Amazu, S., Enhancement of colonic drug absorption by the transcellular permeation route, Pharm. Res., 5, 786, 1988.
155. Sasaki, H., Igarashi, Y., Nagano, T., Nishida, K., and Nakamura, J., Different effects of absorption promoters on corneal and conjunctival penetration of ophthalmic β-blockers, Pharm. Res., 12, 1146, 1995.
156. Green, K. and Tønjum, A., Influence of various agents on corneal permeability, Am. J. Ophthalmol., 72, 897, 1971.
157. Pfister, R. R. and Burstein, N., The effects of ophthalmic drugs, vehicles, and preservatives on corneal epithelium: A scanning electron microscope study, Invest. Ophthalmol., 15, 246, 1976.
158. Godbey, R. E., Green, K., and Hull, D. S., Influence of cetylpyridinium chloride on corneal permeability to penicillin, J. Pharm. Sci., 68, 1176, 1979.
159. Green, K., The effects of preservatives on corneal permeability of drugs, in Biopharmaceutics of Ocular Drug Delivery, Edman, P., Ed., Boca Raton: CRC Press, 1993.
160. Sasaki, H., Nagano, T., Yamamura, K., Nishida, K., and Nakamura, J., Ophthalmic preservatives as absorption promoters for ocular drug delivery, J. Pharm. Pharmacol., 47, 703, 1995.
161. Camber, O. and Edman, P., Influence of some preservatives on the corneal permeability of pilocarpine and dexamethasone, in vitro, Int. J. Pharm., 39, 229, 1987.
162. Sasaki, H., Tei, C., Nishida, K., and Nakamura, J., Effect of opthamic preservatives on serum concentration and local irritation of ocularly applied insulin, Biol. Pharm. Bull., 18, 169, 1995.
163. Podder, S. K., Moy, K. C., and Lee, V. H. L., Improving the safety of topically applied timolol in the pigmented rabbit through manipulation of formulation composition, Exp. Eye Res., 54, 747, 1992.
164. Smolen, V. F., Clevenger, J. M., Williams, E. J., and Bergdolt, M. W., Biophasic availability of ophthalmic carbachol, I. Mechanisms of cationic polymer-and surfactant-promoted miotic activity, J. Pharm. Sci., 62, 958, 1973.
165. Burton, G. D. and Hill, R. M., Aerobic responses of the cornea to ophthalmic preservatives, measured in vivo, Invest. Ophthalmol. Vis. Sci., 21, 842, 1981.
166. Green, K. and Tønjum, A. M., The effect of benzalkonium chloride on the electropotential of the rabbit cornea, Acta Ophthalmol., 53, 348, 1975.
167. Burstein, N. L., Preservative alteration of corneal permeability in humans and rabbits, Invest. Ophthalmol. Vis. Sci., 25, 1453, 1984.
168. Yamashita, S., Saitoh, H., Nakanishi, K., Masada, M., Nadai, T., and Kimura, T., Characterization of enhanced intestinal permeability; electrophysicological study on the effects of diclofenac and ethylenediaminetetraacetic acid, J. Pharm. Pharmacol., 37, 512, 1985.
169. Fix, J. A., Porter, P. A., and Leppert, P. S., Involvement of active sodium transport in the rectal absorption of gentamicin sulfate in the presence and absence of absorption-promoting adjuvants, J. Pharm. Sci., 72, 1134, 1983.
170. Röjanasakul, Y., Liaw, J., and Robbinson, J. R., Mechanisms of action of some penetration enhancers in the cornea: Laser scanning confocal microscopic and electrophysiology studies, Int. J. Pharm., 66, 131, 1990.
171. Collin, H. B., Ultrastractural changes to corneal stromal cells due to ophthalmic preservatives, Act a Opthalmol., 64, 72, 1986.
172. Grass, G. M., Wood, R. W., and Robinson, J. R., Effects of calcium chelating agents on corneal permeability, Invest. Ophthalmol. Vis. Sci., 26, 110, 1985.
173. Ashton, P., Diepold, R., Platzer, A., and Lee, V. H., The effect of chlorhexidine acetate on the corneal penetration of sorbitol from an arnolol forumation in the albino rabbit, J. Ocul. Pharmacol., 6, 37, 1990.
174. Sasaki, H., Yamamura, K., Tei, C., Nishida, K., and Nakamura, J., Ocular permeability of FITC-dextran with absorption promoter for ocular delivery of peptide drug, J. Drug Target., 3, 129, 1995.
175. Ismail, I. M., Chen, C.-C., Richman, J. B., Andersen, J. S., and Tand-Liu, D. D.-S., Comparison of Azone and hexamethylene lauramide in toxicologic effects and penetration enhancement of cimetidine in rabbit eyes, Pharm. Res., 9, 817, 1992.
176. Newton, C., Gebhardt, B. M., and Kaufman, H. E., Topically applied cyclosporine in Azone prolongs corneal allograft survival, Invest. Ophthalmol. Vis. Sci., 29, 208, 1988.
177. Tang-Liu, D. D., Richman, J. B., Weinkam, R. J., and Takruri, H., Effects of four penetration enhancers on corneal permeability of drugs in vitro, J. Pharm. Sci., 83, 85, 1994.
178. Rajewski, R. A. and Stella, V. J., Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery, J. Pharm. Sci., 85, 1142, 1996.
179. Sasamoto, Y., Hirose, S., Ohno, S. Onoe, K., and Matsuda, H., Topical application of ciclosporin ophthalmic solution containing α-ciclodextrin in experimental uveitis, Ophthalmologica, 203, 118, 1991.
180. Jansen, T., Xhonneux, B., Mesens, J., and Borgers, M., β-Cyclodextrins as vehicles in eye-drop formulations: An evaluation of their effects on rabbit corneal epithelium., Lens Eye Toxic. Res., 7., 459, 1990.
181. Pillion, D. J., Amsden, J. A., Kensil, C. R., and Reccia, J., Structure-function relationship among Quillaja saponins serving as excipients for nasal and ocular delivery of insulin, J. Pharm. Sci., 85, 518, 1996.
182. Grossman, R. E., Chu, D. F., and Lee, D. A., Regional ocular gentamicin levels after transcorneal and transscleral iontophoresis, Invest. Ophthalmol. Vis. Sci., 31, 909, 1990.
183. Sarraf, D. and Lee, D. A., The role of iontophoresis in ocular drug delivery, J. Ocul. Pharmacol., 10, 69, 1994.
184. Barza, M., Peckman, C., and Baum, J., Transscleral iontophoresis of gentamicin in monkeys, Invest. Ophthalmol. Vis. Sci., 28, 1033, 1987.
185. Sarraf, D., Equi, R. A., Holland, G. N., Yoshizumi, M. O., and Lee, D. A., Transscleral iontophoresis of foscarnet, Am. J. Ophthalmol., 115, 748, 1993.
186. Hughes, L. and Maurice, D. M., A fresh look at iontophoresis, Arch. Ophthalmol., 102, 1825, 1984.
187. Hill, J. M., Park, N.-H., Gangarosa, L. P., Hull, D. S., Tuggle, C. L., Bowman, K., and Green, K., Iontophoresis of vidarabine monophosphate into rabbit eyes, Invest. Ophthalmol. Vis. Sci., 17, 473, 1978.
188. Rootman, D. S., Jantzen, J. A., Gonzalez, J. R., Fischer, M. J., Beuerman, R., and Hill, J. M., Pharmacokinetics and safety of transcorneal iontophoresis of tobramycin in the rabbit, Invest. Ophthalmol. Vis. Sci., 29, 1397, 1988.
189. Choi, T. B. and Lee, D. A., Transscleral and transcorneal iontophoresis of vancomycin in rabbit eyes, J. Ocul. Pharmacol., 4, 153, 1988.
190. Grossman, R. and Lee, D. A., Transscleral and transcorneal iontophoresis of ketoconazole in the rabbit eye, Ophthalmology, 96, 724, 1989.
191. Hobden, J. A., Rootman, D. S., O'Callaghan, R. J., and Hill, J. M.,
192. Burstein, N. L., Leopold, I. H., and Bernacchi, D. B., Trans-scleral iontophoresis of gentamicin, J. Ocul. Pharmacol., 1, 363, 1985.
193. Barza, M., Peckman, C., and Baum, J., Transscleral iontophoresis of cefazolin, ticarcillin, and gentamicin in the rabbit, Ophthalmology, 93, 133, 1986.
194. Church, A. L., Barza, M., and Baum, J., An improved apparatus for transscleral iontophoresis of gentamicin, Invest. Ophthalmol. Vis. Sci., 33, 3543, 1992.
195. Yoshizumi, M. O., Cohen, D., Verbukh, I., Leinwand, M., Kim, J., and Lee, D. A., Experimental transscleral iontophoresis of ciprofloxacin, J. Ocul. Pharmacol., 7, 163, 1991.
196. Barza, M., Peckman, C., and Baum, J., Transscleral iontophoresis as an adjunctiva treatment for experimental endophthalmitis, Arch. Ophthalmol., 105, 1418, 1987.
197. Miyazaki, S., Mizuoka, H., Oda, M., and Takada, M., External control of drug release and penetration: Enhancement of the transdermal absorption of indomethacin by ultrasound irradiation, J. Pharm. Pharmacol., 43, 115, 1991.
198. Bommannan, D., Okuyama, H., Stauffer, P., and Guy, R. H., Sonophoresis, I. The use of high-frequency ultrasound to enhance transdermal drug delivery, Pharm. Res., 9, 559, 1992.