Safety Evaluation of Ocular Drug Delivery Products: Techniques and Practical Concerns

 Essay regarding Safety Evaluation of Visual Drug Delivery Formulations: Approaches and Useful Considerations

Toxicologic Pathology Basic safety Evaluation of Ocular Medication Delivery Formulations: Techniques and Practical Things to consider Brian G. Short Toxicol Pathol 08; 36; forty-nine DOI: 10. 1177/0192623307310955 The web version of the article can be found at:

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Toxicologic Pathology, 36: 49-62, 2008 Copyright laws В© 08 by World of Toxicologic Pathology ISSN: 0192-6233 print / 1533-1601 online DOI: 10. 1177/0192623307310955

Safety Evaluation of Visual Drug Delivery Formulations: Methods and Functional Considerations BRIAN G. SHORT From Allergan, Inc., Irvine, California, USA. ABSTRACT Advancement new drug candidates and novel delivery techniques for treatment of ocular illnesses has recently faster. Treatment of anteriorsegment diseases provides witnessed advances in prodrug formulations and permeability enhancers. Intravitreal, subconjunctival, and periocular routes of administration and sustained-release products of nanoparticles and microparticles, as well as nonbiodegradable and eco-friendly implants to supply drugs to the posterior portion of the eye, are becoming popular therapeutic methods. Without sufficient regulatory insight into ocular drugs, such routes of operations and new formulations can pose unique challenges to those involved with designing nonclinical programs, which include considering scientific and non-clinical factors and choosing species, strains, and ocular degree of toxicity parameters. Toxicologic pathologists likewise contribute working experience to considering morphological effects of these book formulations. Finally, understanding species' anatomical differences is useful pertaining to interpreting toxicological and pathological responses to the eye which is important for individual risk assessment of these significant new solutions for ocular diseases. Keywords: Ocular medicine delivery; intravitreal; subconjunctival; periocular; ocular implant.

INTRODUCTION Millions of people suffer from a wide variety of ocular diseases, many of which usually lead to visible impairment and ocular blindness and expense the federal government about $4 billion annually (Clark and Yorio, 2003). Certain ocular disorders are quite unusual, whereas others, such as cataracts, age-related macular degeneration (AMD), and glaucoma, are very common, especially in the ageing population (Table 1). A rapid expansion of recent technologies in ocular drug delivery and new medicine candidates, including biologics, to treat these difficult diseases inside the anterior and posterior sectors of the vision have recently emerged. These kinds of approaches are necessary because the eyesight has many one of a kind barriers to drug delivery (Figure 1). Current routes of government include tend to be not restricted to topical operations, systemic administration, intravitreal shots, and intraocular implants, each of which has its own set of issues and disadvantages (Figure 2). Visual bioavailability after topical visual eyedrop operations, the most common type of ocular medicine , is less than 5% and often below 1%, and for that reason, only the conditions of the anterior segment of the eye can usually be treated with eyedrops. Blood-ocular obstacles, Address correspondence to: Brian G. Short, Allergan, Inc., 2525 Dupont Dr . RD-2A, Irvine, CALIFORNIA 92612. Short-hand: AMD, age-related macular deterioration; CNTF, ciliary neurotrophic factor; DDS, medication delivery program; ECT, encapsulated cell technology; ERG, electroretinogram; EVA, ethylene vinyl acetate; FIHS,...

Sources: Aronin, N. (2006). Goal selectivity in mRNA silencing. Gene Ther 13, 509-16. Avalos, M., Jacobs, A., and Wilkin, J. E. (1997). Toxicity testing pertaining to ocular medication products. In Advances in Ocular Toxicology (K. Green et ing., eds., pp. 261-8). Plenum, New York. Bourges, J. D., Bloquel, C., Thomas, A., Froussart, N., Bochot, A., Azan Farreneheit., Gurny, 3rd there’s r., BenEzra, M., and Behar-Cohen, F. (2006) Intraocular implants for extended medicine delivery: healing applications. Adv Drug Deliv Rev 54.99, 1182-1202. Bourges, J. L., Gautier, T. E., Delie, F., Bejjani, R. A., Jeanny, M., Gurny, Ur., BenEzra, M., and Behar-Cohen, F. (2003). Ocular medicine delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Opth Am?iais Sci forty-four, 3562-9. Clark, A. Farreneheit, and Yorio, T. (2003). Ophthalmic drug discovery. Characteristics Rev 2, 448-59. Davis, J. M., Gilger, M. C., and Robinson, M. R. (2004). Novel ways to ocular medication delivery. Curr Opin Mol Therap 6th: 195-205. Dureau, P., Bonnel, S., Menasche, M., Dufier, J. T., and Abitbol, M. (2001). Quantitative research of intravitreal injections in the rat. Curr Eye Ers 22, 74-7. Eljarrat-Binstock, Elizabeth., and Domb, A. T. (2006). Iontophoresis: a noninvasive ocular medication delivery. T Controlled Release 110, 479-89. Fattal, Electronic., and Bochot, A. (2006). Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers, and siRNA. Adv Drug Deliv Revolution 58, 1203-23. Ferrara, N., Damico, M., Shams, In., Lowman, H., and Betty, R. (2006). Development of ranibizumab, an anti-vascular endothelial progress factor antigen binding fragment, as therapy for neovascular age-related deshonrar degeneration. Retina 26, 859-70. Friedrich, T. (2003). Mathematical modeling of drug distribution in the vitreous humor. In Ophthalmic Medication Delivery Devices (A. E. Mitra, impotence., p. 195). Marcel Dekker, New York. Ghate, D., and Edelhauser, H. F. (2006). Ocular medicine delivery. Professional Opin Medicine Deliv a few, 275-87.

Downloaded from at School of Aston on Feb 10, 2010




Herrero-Vanrell, 3rd there’s r., and Refojo, M. F. (2001). Eco-friendly microspheres intended for vitreoretinal drug delivery. Adv Drug Deliv 52, 5-16. Heywood R., and Gopinath C. (1990). Morphological examination of image function. Tox Path 18, 204-217. The netherlands, J. Meters. (2005). Morphometric comparisons among cynomolgus apes and NZW rabbit sight: implications pertaining to intravitreal pelerine studies. Info on file, Allergan, Incorporation, Irvine, FLORIDA. Hsu, M. (2007). Drug delivery options for posterior part disease. Curr Opin Ophthalmol 18, 235-9. Jaffe, G. L., Matn, D., Callanan, D., Pearson, A., Garnishment, B., Comsock, T., and Fluocinolone Acetonide Study Group. (2006). Fluocinolone acetonide: implant (retisert) to get noninfectious detras uveitis. Ophthalmology 113, 1020-7. Kim, H., Csaky, T. G., Gilger, B. C., Dunn, J. P., Lee, S. T., Tremblay, M., De Abadia, F., Tansey, G., Yuan, P., Bungay, P. M., Lutz, 3rd there’s r. J., and Robinson, Meters. R. (2005). Preclinical analysis of a book episcleral cyclosporine implant for ocular graft-versus-host disease. Spend Ophthalmol Am?iais Sci 46, 655-62. Kim, H., Csaky, K. G., Gravlin, M., Yuan, P., Lutz, L. J., Bungay, P. Meters., Tansey, G., De Monasterio, F., Potti, G. E., Grimes, G., and Johnson, M. 3rd there’s r. (2006). Safety and pharmcokinetics of a preservative-free triamcinolone acetonide formulation pertaining to intraitreal operations. Retina 21, 523-30. Koch, F., and Kreiger, A. (1994). A mild and electron microscopic analyze of the treatment of pendant plana incisions in the rhesus monkey. Graefe's Arch Clin Exp Ophthalmol 232, 47-56. Kuppermann, W. D., Blumendranz, M. S i9000., Haller, L. A., Williams, G. A., Weinberg, G. V., Noir, C., and Whitcup, S. M. (2007). Randomized managed study of an intravitreous dexamethasone drug delivery system in patients with persistent deshonrar edema. Arch Ophthalmol 125, 309-17. Latendresse, J. L., Warbrittion, A. R, Jonassen, H., and Creasy, Deb. M. (2002). Fixation of testes and eye by using a modified Davison's fluid: assessment with Bouin's fluid and conventional Davidson's fluid. Toxicol Pathol 31, 524-33. Leblanc, B., Jezequel, S., Davies, T., Hanton, G., and Taradach, C. (1998). Holding of drugs to eye melanin is not predictive of ocular toxicity. Reg Toxicol Pharmacol 28, 124-132. Leeds, J. Meters., Henry, H. P., Bistner, S., Scherrill, S., Williams, K., and Levin, A. A. (1998). Pharmacokinetics associated with an antisense oligonucleotide injected intravitreally in apes. Drug Metab Dispos twenty six, 670-5. Leeds, J. M., Henry, S i9000. P., Truong, L., Zutshi, A., Levin, A. A., and Kornbrust, D. (1997). Pharmacokinetics of your potential man cytomegalovirus beneficial, a phosphorothioate oligonucleotide, following intravitreal shot in the rabbit. Drug Metab Dispos twenty-five, 921-6. Lucentis (ranibizumab) Pharmacology Review (2006). Retrieved May 22, 3 years ago, from [email protected] Web site, 125156s0000_Lucentis_PharmR. pdf format Macugen (pegaptanib sodium) Pharmacology Review (2004). Retrieved Might 22, 2007, from [email protected] Web site, 21-756_Macugen_pharmr. pdf file McGee, G. H., Dembinska, O., and Gruebbel, Meters. (2005). Analysis of triamcinolone acetonide following intravitreal treatment in Fresh Zealand white colored rabbits. Int J Toxicol 24, 419-25. Micera, A., Stampachiacchiere, N., Aronni, H., Serapiao dos Santos, Meters., and Lambiase, A. (2005). Toll-like receptors and the attention. Curr Opin Allergy Clin Immunol your five, 451-8.

Morris, B., Imrie, F., Armbrecht, A., and Dhillon, B. (2007). Age-related macular deterioration and recent innovations: new optimism old eyes? Postgrad Mediterranean J 83, 301-7. Morrison, V. T., Koh, They would. J., Cheng, L., Bessho, K., Davison, M. C., and Freeman, W. L. (2006). Intravitreal toxicity from the kenalog automobile (benzyl alcohol) in rabbits. Retina 26, 339-44. Myles, M. At the., Neumann, Deb. M., and Hill, M. M. (2005). Recent improvement in ocular drug delivery for trasero segment disease: emphasis on transcleral iontophoresis. Adv Drug Deliv Rev 57, 2063-79. Ng, E. T., and Adamis, A. P. (2006). Anti-VEGF aptamer (pegaptanib) therapy intended for ocular vascular diseases. Ann N Sumado a Acad Sci 1082, 151-71. Okabe, T., Kimura, L., Kunou, And., Okabe, T., Kato, A., and Ogura, Y. (2003). Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate. Invest Ophthalmol Visual Sci 44, 740-4. Pearson, S. A., Jaffe, G. J., Martin, M. F., Cordahi, G. J., Grossniklaus, H., Schmeisser, Electronic. T., and Ashton, P. (1996). Analysis of a delivery system offering long-term release of cyclosporine. Arch Ophthalmol 114, 311-7. Perry, C. M., and Balfour, M. A. (1999). Fomiversen. Prescription drugs 57, 375-80. Retisert (Fluocinolone Acetonide Intravitreal Implant) Pharmacology Review (2004). Retrieved May 22, 3 years ago, from [email protected] Web site, http://www. fda. gov/cder/foi/nda/2005/021737s000_PharmR. pdf Samuelson, D. A. (1999). Ophthalmic anatomy. In Veterinary Ophthalmology (3rd model, K. Gelatt, ed., s. 111). Lippincott Williams & Wilkins, Philadelphia, PA. Sinha, D. L., Cartwright, M. E., and Johnson, L. C. (2006). Incidental mononuclear cell imbed in the uvea of cynomolgus monkeys. Toxicol Pathol thirty four, 148-51. Jones, T. M., Pearson, A., Blandford, Deb. L., Brown, J. G., Goins, E. A., Hollins, J. D., Schmeisser, At the. T., Glavinos, P., Baldwin, L. B., and Ashton, P. (1992). Intravitreal sustained-release ganciclovir. Arch Ophthalmol one hundred ten, 255-8. Tao, W. (2006). Application of encapsulated cell technology for retinal degenerative conditions. Expert Opin Biol Ther 6, 717-26. Theng, L. T. T., Ei, Big t. S., Zhou, L., Lam, K. Watts., and Chee, S. G. (2003). Pharmacokinetic and degree of toxicity study of your intraocular cyclosporine DDS in the anterior segment of rabbit eyes. Commit Ophthalmol Aesthetic Sci forty-four, 4895-9. Vitravene (fomiversen) Pharmacology/Toxicology Review and Evaluation (1998). Retrieved May well 22, 3 years ago, from [email protected] Web site http://www. fda. gov/cder/foi/nda/98/20961_Vitravene_pharmr. pdf Weir, A., Rooms, W., Chen, C., Chen, Z., Mukherjee, A., and Yang, L. (1999). Things to consider for the nonclinical advancement intravitreal medication products. Toxicologist 18, 323 (Abstract 1524). Whiteley, H. E., and Peiffer, Ur. L. (2002). The eye. In Handbook of Toxicologic Pathology (2nd impotence., W. Meters. Haschek, C. G. Rousseaux, and M. A. Wallig, eds., pp. 539-84). Academics Press, Hillcrest, CA. Yasukawa, T., Ogura, Y., Kimura, H., Sakurai, E., and Tabata, Con. (2006). Drug delivery coming from ocular enhancements. Expert Opin Drug Deliv 3, 261-73. Younis, H. S., Picotti, J. R., Slim, R. M., Joniken, M., Burns-Nass, L. A., Heward, J., and Evering, W. (2007). Safety assessment of a VEGF receptor tyrosine kinase inhibitor, AG-023845, in cynomolgus apes following sub-Tenon ocular operations. Poster demonstration, 8th Clinical Meeting with the Association to get Ocular Pharmacology, February 9-11, San Diego, LOS ANGELES.

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