DOI QR코드

DOI QR Code

A Novel Approach of Drug Delivery via Intrascleral Implantation of Latanoprost Imbedded Disk

  • Moon, Soo-Jin (Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University) ;
  • Seo, Min-Soo (Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Kang, Kyung-Ku (Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Sung, Soo-Eun (Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Yun, Sungho (Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University) ;
  • Kwon, Young-Sam (Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2019.03.25
  • Accepted : 2019.08.07
  • Published : 2019.08.30

Abstract

This study evaluates the drug delivery and biocompatibility of latanoprost imbedded disk in rabbit eye by assessing pharmacokinetics (PK), clinical signs, and histopathologic findings. During 84 days of experimental period, 48 New Zealand Rabbit (NZW) eyes were divided into control group which received no treatment and test material group which latanoprost were implanted intrasclerally. Pharmacokinetic assessment was performed to evaluate the drug delivery for 3 months. For biocompatibility, clinical signs were observed and histopathological analysis was done at 3 months post-operatively. The concentration of latanoprost in the iris tissue was maintained during the experimental period and the highest level of latanoprost was found at 4 weeks. However, the latanoprost was not found in the aqueous humor. Macroscopically, there was no evidence of clinical signs except for temporary hyperemia, neovascularization and edema immediately after surgery. On histopathological examination, there were no abnormal findings such as hyperemia, neovascularization, and edema in the eye tissues. The latanoprost imbedded disks has effectively released the drug into the adjacent tissue with high compatibility. Therefore, this study suggests that the drug delivery system with intrascleral latanoprost imbedded implants might be a novel approach as a treatment option for glaucoma.

Keywords

References

  1. Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Scandinavian Latanoprost Study Group. Ophthalmology 1995; 102: 1743-1752. https://doi.org/10.1016/S0161-6420(95)30798-1
  2. Ambati J, Canakis CS, Miller JW, Gragoudas ES, Edwards A, Weissgold DJ, Kim I, Delori FC, Adamis AP. Diffusion of high molecular weight compounds through sclera. Invest Ophth Vis Sci 2000; 41: 1181-1185.
  3. Azarmi S, Tao X, Chen H, Wang ZL, Finlay WH, Lobenberg R, Roa WH. Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles. Int J Pharm 2006; 319: 155-161. https://doi.org/10.1016/j.ijpharm.2006.03.052
  4. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems--recent advances. Prog Retin Eye Res 1998; 17: 33-58. https://doi.org/10.1016/S1350-9462(97)00002-5
  5. Bras D, Maggio F. Surgical Treatment of Canine Glaucoma: Cyclodestructive Techniques. Vet Clin North Am Small Anim Pract 2015; 45: 1283-1305. https://doi.org/10.1016/j.cvsm.2015.06.007
  6. Camras CB. Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma: a six-month masked, multicenter trial in the United States. The United States Latanoprost Study Group. Ophthalmology 1996; 103: 138-147. https://doi.org/10.1016/S0161-6420(96)30749-5
  7. Camras CB, Alm A, Watson P, Stjernschantz J. Latanoprost, a prostaglandin analog, for glaucoma therapy. Efficacy and safety after 1 year of treatment in 198 patients. Latanoprost Study Groups. Ophthalmology 1996; 103: 1916-1924. https://doi.org/10.1016/S0161-6420(96)30407-7
  8. Elzoghby AO, Samy WM, Elgindy NA. Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Release 2012; 157: 168-182. https://doi.org/10.1016/j.jconrel.2011.07.031
  9. Freddo TF, Sacks-Wilner R. Interendothelial junctions of the rabbit iris vasculature in anterior uveitis. Invest Ophthalmol Vis Sci 1989; 30: 1104-1111.
  10. Geroski DH, Edelhauser HF. Transscleral drug delivery for posterior segment disease. Adv Drug Deliv Rev 2001; 52: 37-48. https://doi.org/10.1016/S0169-409X(01)00193-4
  11. Gilger BC, Mandal A, Shah S, Mitra AK. Episcleral, intrascleral, and suprachoroidal routes of ocular drug delivery - recent research advances and patents. Recent Pat Drug Deliv Formul 2014; 8: 81-91. https://doi.org/10.2174/187221130802140707093509
  12. Jessen BA, Shiue MH, Kaur H, Miller P, Leedle R, Guo H, Evans M. Safety assessment of subconjunctivally implanted devices containing latanoprost in Dutch-belted rabbits. J Ocul Pharmacol Ther 2013; 29: 574-585. https://doi.org/10.1089/jop.2012.0190
  13. Lee SB, Geroski DH, Prausnitz MR, Edelhauser HF. Drug delivery through the sclera: effects of thickness, hydration, and sustained release systems. Experimental Eye Research 2004; 78: 599-607. https://doi.org/10.1016/S0014-4835(03)00211-2
  14. Lee SS, Burke J, Shen J, Almazan A, Orilla W, Hughes P, Zhang J, Li H, Struble C, Miller PE, Robinson MR. Bimatoprost sustained-release intracameral implant reduces episcleral venous pressure in dogs. Vet Ophthalmol 2018; 21: 376-381. https://doi.org/10.1111/vop.12522
  15. Majorek KA, Porebski PJ, Dayal A, Zimmerman MD, Jablonska K, Stewart AJ, Chruszcz M, Minor W. Structural and immunologic characterization of bovine, horse, and rabbit serum albumins. Mol Immunol 2012; 52: 174-182. https://doi.org/10.1016/j.molimm.2012.05.011
  16. Maurice DM, Polgar J. Diffusion across the sclera. Exp Eye Res 1977; 25: 577-582. https://doi.org/10.1016/0014-4835(77)90136-1
  17. McLaurin E, Cavet ME, Gomes PJ, Ciolino JB. Brimonidine Ophthalmic Solution 0.025% for Reduction of Ocular Redness: A Randomized Clinical Trial. Optom Vis Sci 2018; 95: 264-271. https://doi.org/10.1097/OPX.0000000000001182
  18. Miller PE, Bentley E. Clinical Signs and Diagnosis of the Canine Primary Glaucomas. Vet Clin North Am Small Anim Pract 2015; 45: 1183-1212. https://doi.org/10.1016/j.cvsm.2015.06.006
  19. Okabe J, Kimura H, Kunou N, Okabe K, Kato A, Ogura Y. Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate. Invest Ophthalmol Vis Sci 2003; 44: 740-744. https://doi.org/10.1167/iovs.02-0375
  20. Olsen TW, Edelhauser HF, Lim JI, Geroski DH. Human scleral permeability. Effects of age, cryotherapy, transscleral diode laser, and surgical thinning. Invest Ophthalmol Vis Sci 1995; 36: 1893-1903.
  21. Olsen TW, Aaberg SY, Geroski DH, Edelhauser HF. Human sclera: Thickness and surface area. Am J Ophthalmol 1998;125: 237-241. https://doi.org/10.1016/S0002-9394(99)80096-8
  22. Pereira FQ, Bercht BS, Soares MG, da Mota MG, Pigatto JA. Comparison of a rebound and an applanation tonometer for measuring intraocular pressure in normal rabbits. Vet Ophthalmol 2011; 14: 321-326. https://doi.org/10.1111/j.1463-5224.2011.00879.x
  23. Rubino OP, Kowalsky R, Swarbrick J. Albumin Microspheres as a Drug-Delivery System - Relation among Turbidity Ratio, Degree of Cross-Linking, and Drug-Release. Pharmaceut Res 1993; 10: 1059-1065. https://doi.org/10.1023/A:1018979126326
  24. Schoenwald RD, Deshpande GS, Rethwisch DG, Barfknecht CF. Penetration into the anterior chamber via the conjunctival/scleral pathway. J Ocul Pharmacol Th 1997; 13: 41-59. https://doi.org/10.1089/jop.1997.13.41
  25. Teich SA, Walsh JB. A grading system for iris neovascularization. Prognostic implications for treatment. Ophthalmology 1981; 88: 1102-1106. https://doi.org/10.1016/S0161-6420(81)34900-8
  26. Wang X, Dong J, Wu Q. Twenty-four-hour measurement of IOP in rabbits using rebound tonometer. Vet Ophthalmol 2013; 16: 423-428. https://doi.org/10.1111/vop.12020