Trans-scleral ocular drug delivery for the treatment of posterior segment eye diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Xiaoli ,  Cheng Lingyun

Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, China;

Corresponding author：

Cheng Lingyun, Email: lingyunc@hotmail.com

Keywords：

Administration, ophthalmic; Sclera; Delayed-action preparations/therapeutic use; Posterior eye segment; Review

DOI：

10.3760/cma.j.issn.1005-1015.2017.02.028

Video：

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Abstract Full text Figures/Tables Video References Cited by

The human sclera accounts for 95% of the surface of the eyeball, providing ample contact area which is suitable for targeted trans-scleral ocular drug delivery. Currently there are several tans-scleral sustained-release strategies, including intra-scleral delivery, episcleral delivery, as well as tans-scleral iontophoresis. Different devices and methods have their own advantages and disadvantages, for example, intra-scleral delivery is somehow invasive, and episcleral delivery device needs to be made thin to prevent erosion of conjunctiva, iontophoresis needs to be frequently repeated as of its short-term effect. With the development of bio-material engineering technology, episcleral microfilm could become an ideal drug delivery route for posterior segment ocular diseases.

Citation： Li Xiaoli, Cheng Lingyun. Trans-scleral ocular drug delivery for the treatment of posterior segment eye diseases. Chinese Journal of Ocular Fundus Diseases, 2017, 33(2): 213-217. doi: 10.3760/cma.j.issn.1005-1015.2017.02.028 Copy

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2.	Kamei M, Misono K, Lewis H. A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits[J]. Am J Ophthalmol, 1999, 128(6): 739-746.
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8.	Nagai N, Kaji H, Onami H, et al. A polymeric device for controlled transscleral multi-drug delivery to the posterior segment of the eye[J]. Acta Biomater, 2014, 10(2): 680-687. DOI: 10.1016/j.actbio.2013.11.004.
9.	Kawashima T, Nagai N, Kaji H, et al. A scalable controlled-release device for transscleral drug delivery to the retina[J]. Biomaterials, 2011, 32(7): 1950-1956. DOI: 10.1016/j.biomaterials.2010.11.006.
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11.	Kuno N, Fujii S. Biodegradable intraocular therapies for retinal disorders: progress to date[J]. Drugs Aging, 2010, 27(2): 117-134. DOI: 10.2165/11530970-000000000-00000.
12.	Lee SS, Hughes P, Ross AD, et al. Biodegradable implants for sustained drug release in the eye[J]. Pharm Res, 2010, 27(10): 2043-2053. DOI: 10.1007/s11095-010-0159-x.
13.	Meng Y, Sun S, Li J, et al. Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-epsilon-caprolactone matrix[J]. Acta Biomater, 2014, 10(1): 126-133. DOI: 10.1016/j.actbio.2013.09.022.
14.	Sun S, Li J, Li X, et al. Episcleral drug film for better-targeted ocular drug delivery and controlled release using multilayered poly-epsilon-caprolactone (PCL)[J]. Acta Biomater, 2016, 37: 143-154. DOI: 10.1016/j.actbio.2016.04.014.
15.	Shin JP, Park YC, Oh JH, et al. Biodegradable intrascleral implant of triamcinolone acetonide in experimental uveitis[J]. J Ocul Pharmacol Ther, 2009, 25(3): 201-208. DOI: 10.1089/jop. 2008.0086.
16.	Lin CC, Anseth KS. PEG hydrogels for the controlled release of biomolecules in regenerative medicine[J]. Pharm Res, 2009, 26(3): 631-643. DOI: 10.1007/s11095-008-9801-2.
17.	Li X, Wang Y, Yang C, et al. Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy[J]. Nanoscale, 2014, 6(23): 14488-14494. DOI: 10.1039/c4nr04761c.
18.	Pescina S, Ferrari G, Govoni P, et al. In-vitro permeation of bevacizumab through human sclera: effect of iontophoresis application[J]. J Pharm Pharmacol, 2010, 62(9): 1189-1194. DOI: 10.1111/j.2042-7158.2010.01153.x.
19.	Souied EH, Reid SN, Piri NI, et al. Non-invasive gene transfer by iontophoresis for therapy of an inherited retinal degeneration[J]. Exp Eye Res, 2008, 87(3): 168-175. DOI: 10.1016/j.exer.2008.04.009.
20.	Eljarrat-Binstock E, Domb AJ, Orucov F, et al. In vitro and in vivo evaluation of carboplatin delivery to the eye using hydrogel-iontophoresis[J]. Curr Eye Res, 2008, 33(3): 269-275. DOI: 10.1080/02713680701871140.
21.	Eljarrat-Binstock E, Orucov F, Aldouby Y, et al. Charged nanoparticles delivery to the eye using hydrogel iontophoresis[J]. J Control Release, 2008, 126(2): 156-161. DOI: 10.1016/j.jconrel. 2007.11.016.
22.	Chopra P, Hao J, Li SK. Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera[J]. J Control Release, 2012, 160(1): 96-104. DOI: 10.1016/ j.jconrel.2012.01.032.
23.	Chopra P, Hao J, Li SK. Iontophoretic transport of charged macromolecules across human sclera[J]. Int J Pharm, 2010, 388(1-2): 107-113. DOI: 10.1016/j.ijpharm.2009.12.046.
24.	Eljarrat-Binstock E, Pe'er J, Domb AJ. New techniques for drug delivery to the posterior eye segment[J]. Pharm Res, 2010, 27(4): 530-543. DOI: 10.1007/s11095-009-0042-9.
25.	Parkinson TM, Ferguson E, Febbraro S, et al. Tolerance of ocular iontophoresis in healthy volunteers[J]. J Ocul Pharmacol Ther, 2003, 19(2): 145-151. DOI: 10.1089/108076803321637672.
26.	Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery[J]. J Control Release, 2006, 110(3): 479-489. DOI: 10.1016/j.jconrel.2005.09.049.
27.	Lafond M, Aptel F, Mestas JL, et al. Ultrasound-mediated ocular delivery of therapeutic agents: a review[J]. Expert Opin Drug Deliv, 2016, 27: 1-12. DOI: 10.1080/17425247.2016.1198766.
28.	Murugappan SK, Zhou Y. Transsclera drug delivery by pulsed high-intensity focused ultrasound (HIFU): an ex vivo study[J]. Curr Eye Res, 2015, 40(11): 1172-1180. DOI: 10.3109/02713683. 2014.980006.
29.	Razavi A, Clement D, Fowler RA, et al. Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery[J]. Ultrasound Med Biol, 2014, 40(6): 1216-1227. DOI: 10.1016/j.ultrasmedbio.2013.12.032.
30.	Suen WL, Wong HS, Yu Y, et al. Ultrasound-mediated transscleral delivery of macromolecules to the posterior segment of rabbit eye in vivo[J]. Invest Ophthalmol Vis Sci, 2013, 2654(6): 4358-4365. DOI: 10.1167/iovs.13-11978.
31.	Huang D, Wang L, Dong Y, et al. A novel technology using transscleral ultrasound to deliver protein loaded nanoparticles[J]. Eur J Pharm Biopharm, 2014, 88(1): 104-115. DOI: 10.1016/ j.ejpb.2014.04.011.

1. Tsujikawa A. Complications associated with intravitreal injections[J]. Nippon Ganka Gakkai Zasshi, 2014, 118(8): 631-632.
2. Kamei M, Misono K, Lewis H. A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits[J]. Am J Ophthalmol, 1999, 128(6): 739-746.
3. Kim H, Robinson MR, Lizak MJ, et al. Controlled drug release from an ocular implant: an evaluation using dynamic three-dimensional magnetic resonance imaging[J]. Invest Ophthalmol Vis Sci, 2004, 45(8): 2722-2731. DOI: 10.1167/iovs.04-0091.
4. Robinson MR, Lee SS, Kim H, et al. A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide[J]. Exp Eye Res, 2006, 82(3): 479-487. DOI: 10.1016/j.exer.2005.08.007.
5. Okabe K, Kimura H, Okabe J, et al. Ocular tissue distribution of betamethasone after anterior-episcleral, posterior-episcleral, and anterior-intrascleral placement of nonbiodegradable implants[J]. Retina, 2007, 27(6): 770-777. DOI: 10.1097/IAE.0b013e 31802ea591.
6. Kim YM, Lim JO, Kim HK, et al. A novel design of one-side coated biodegradable intrascleral implant for the sustained release of triamcinolone acetonide[J]. Eur J Pharm Biopharm, 2008, 70(1): 179-186. DOI: 10.1016/j.ejpb.2008.04.023.
7. Olsen TW, Aaberg SY, Geroski DH, et al. Human sclera: thickness and surface area[J]. Am J Ophthalmol, 1998, 125(2): 237-241.
8. Nagai N, Kaji H, Onami H, et al. A polymeric device for controlled transscleral multi-drug delivery to the posterior segment of the eye[J]. Acta Biomater, 2014, 10(2): 680-687. DOI: 10.1016/j.actbio.2013.11.004.
9. Kawashima T, Nagai N, Kaji H, et al. A scalable controlled-release device for transscleral drug delivery to the retina[J]. Biomaterials, 2011, 32(7): 1950-1956. DOI: 10.1016/j.biomaterials.2010.11.006.
10. Onami H, Nagai N, Kaji H, et al. Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization[J/OL]. PloS One, 2013, 8(3): 58580 [2013-03-05]. . DOI: 10.1371/journal.pone.0058580.
11. Kuno N, Fujii S. Biodegradable intraocular therapies for retinal disorders: progress to date[J]. Drugs Aging, 2010, 27(2): 117-134. DOI: 10.2165/11530970-000000000-00000.
12. Lee SS, Hughes P, Ross AD, et al. Biodegradable implants for sustained drug release in the eye[J]. Pharm Res, 2010, 27(10): 2043-2053. DOI: 10.1007/s11095-010-0159-x.
13. Meng Y, Sun S, Li J, et al. Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-epsilon-caprolactone matrix[J]. Acta Biomater, 2014, 10(1): 126-133. DOI: 10.1016/j.actbio.2013.09.022.
14. Sun S, Li J, Li X, et al. Episcleral drug film for better-targeted ocular drug delivery and controlled release using multilayered poly-epsilon-caprolactone (PCL)[J]. Acta Biomater, 2016, 37: 143-154. DOI: 10.1016/j.actbio.2016.04.014.
15. Shin JP, Park YC, Oh JH, et al. Biodegradable intrascleral implant of triamcinolone acetonide in experimental uveitis[J]. J Ocul Pharmacol Ther, 2009, 25(3): 201-208. DOI: 10.1089/jop. 2008.0086.
16. Lin CC, Anseth KS. PEG hydrogels for the controlled release of biomolecules in regenerative medicine[J]. Pharm Res, 2009, 26(3): 631-643. DOI: 10.1007/s11095-008-9801-2.
17. Li X, Wang Y, Yang C, et al. Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy[J]. Nanoscale, 2014, 6(23): 14488-14494. DOI: 10.1039/c4nr04761c.
18. Pescina S, Ferrari G, Govoni P, et al. In-vitro permeation of bevacizumab through human sclera: effect of iontophoresis application[J]. J Pharm Pharmacol, 2010, 62(9): 1189-1194. DOI: 10.1111/j.2042-7158.2010.01153.x.
19. Souied EH, Reid SN, Piri NI, et al. Non-invasive gene transfer by iontophoresis for therapy of an inherited retinal degeneration[J]. Exp Eye Res, 2008, 87(3): 168-175. DOI: 10.1016/j.exer.2008.04.009.
20. Eljarrat-Binstock E, Domb AJ, Orucov F, et al. In vitro and in vivo evaluation of carboplatin delivery to the eye using hydrogel-iontophoresis[J]. Curr Eye Res, 2008, 33(3): 269-275. DOI: 10.1080/02713680701871140.
21. Eljarrat-Binstock E, Orucov F, Aldouby Y, et al. Charged nanoparticles delivery to the eye using hydrogel iontophoresis[J]. J Control Release, 2008, 126(2): 156-161. DOI: 10.1016/j.jconrel. 2007.11.016.
22. Chopra P, Hao J, Li SK. Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera[J]. J Control Release, 2012, 160(1): 96-104. DOI: 10.1016/ j.jconrel.2012.01.032.
23. Chopra P, Hao J, Li SK. Iontophoretic transport of charged macromolecules across human sclera[J]. Int J Pharm, 2010, 388(1-2): 107-113. DOI: 10.1016/j.ijpharm.2009.12.046.
24. Eljarrat-Binstock E, Pe'er J, Domb AJ. New techniques for drug delivery to the posterior eye segment[J]. Pharm Res, 2010, 27(4): 530-543. DOI: 10.1007/s11095-009-0042-9.
25. Parkinson TM, Ferguson E, Febbraro S, et al. Tolerance of ocular iontophoresis in healthy volunteers[J]. J Ocul Pharmacol Ther, 2003, 19(2): 145-151. DOI: 10.1089/108076803321637672.
26. Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery[J]. J Control Release, 2006, 110(3): 479-489. DOI: 10.1016/j.jconrel.2005.09.049.
27. Lafond M, Aptel F, Mestas JL, et al. Ultrasound-mediated ocular delivery of therapeutic agents: a review[J]. Expert Opin Drug Deliv, 2016, 27: 1-12. DOI: 10.1080/17425247.2016.1198766.
28. Murugappan SK, Zhou Y. Transsclera drug delivery by pulsed high-intensity focused ultrasound (HIFU): an ex vivo study[J]. Curr Eye Res, 2015, 40(11): 1172-1180. DOI: 10.3109/02713683. 2014.980006.
29. Razavi A, Clement D, Fowler RA, et al. Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery[J]. Ultrasound Med Biol, 2014, 40(6): 1216-1227. DOI: 10.1016/j.ultrasmedbio.2013.12.032.
30. Suen WL, Wong HS, Yu Y, et al. Ultrasound-mediated transscleral delivery of macromolecules to the posterior segment of rabbit eye in vivo[J]. Invest Ophthalmol Vis Sci, 2013, 2654(6): 4358-4365. DOI: 10.1167/iovs.13-11978.
31. Huang D, Wang L, Dong Y, et al. A novel technology using transscleral ultrasound to deliver protein loaded nanoparticles[J]. Eur J Pharm Biopharm, 2014, 88(1): 104-115. DOI: 10.1016/ j.ejpb.2014.04.011.

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