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Biodegradable Microspheres for Transscleral Drug Delivery |
Shiyu Zhou,Yin Han,Yongchun Meng,Lingyun Cheng |
Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, China |
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Abstract Due to the complex of eye physiology and multiple anatomical barriers, systemically delivered drugs often cannot maintain a sustained drug level in posterior retina and vitreous. Though eye drop is convenient for patients, therapeutics that reaches retina or vitreous is very limited after topical administration. Intravitreal injection is invasive and prone to complications such as lens damage, vitreous bleeding, retinal detachment, and infection. In contrast to these routes of delivery, transscleral drug delivery has advantages such as large surface area, easy access and administration, and better safety profile without breach of the globe integrity.The challenge for transscleral delivery is that the therapeutics delivered onto the episclera needs to have an adequate concentration. If the episcleral concentration is too high, large portion of the delivered drug will be absorbed into systemic circulation and may cause systemic side effects. On the other hand, low episcleral drug concentration cannot build an effective concentration gradient for drug crossing the sclera and reaching choroid and retina. Therefore, many therapeutic compounds are not suited for transscleral delivery. In order to satisfy the proper episcleral concentration, scientists have been modulating the drug dissolution by microspheres or fabricating episcleral devices. Compared with episcleral implant or devices, episcleral microspheres do not need surgical procedure. The microspheres can be administrated by a simple needle injection.
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Received: 02 May 2017
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Fund: This study was funded by National Natural Science Foundation of China (31271022) |
Corresponding Authors:
Lingyun Cheng, Institute of Ocular Pharmacology, School of Ophthalmology and
Optometry, Wenzhou Medical University, Wenzhou 325027, China (Email: lingyunc@hotmail.com)
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|
[1] |
Malhotra S, Khare A, Grover K, et al. Design and Evaluation of Voriconazole Eye Drops for the Treatment of Fungal Keratitis. J Pharm (Cairo), 2014, 2014: 490595. DOI: 10.1155/2014/490595.
|
[2] |
Glogowski S, Lowe E, Sioumermet R, et al. Prolonged exposure to loteprednol etabonate in human tear fluid and rabbit ocular tissues following topical ocular administration of lotemax gel,0.5%. J Ocul Pharmacol Ther, 2014, 30(1): 66-73. DOI: 10.1089/jop.2013.0142.
|
[3] |
Kaufman HE, Haw WH. Ganciclovir ophthalmic gel 0.15%: safety and efficacy of a new treatment for herpes simplex keratitis.Curr Eye Res, 2012, 37(7): 654-660. DOI: 10.3109/02713683.2012.692846.
|
[4] |
Lin J, Sun J, Wang Y, et al. Ocular Pharmacokinetics of Naringenin Eye Drops Following Topical Administration to Rabbits. J Ocul Pharmacol Ther, 2015, 31(1): 51-56. DOI: 10.1089/jop.2014.0047.
|
[5] |
Boddu SH, Gupta H, Patel S. Drug delivery to the back of the eye following topical administration: an update on research and patenting activity. Recent Pat Drug Deliv Formul, 2014, 8(1):27-36. DOI: 10.2174/1872211308666140130093301.
|
[6] |
Chen Q, Zheng Y, Li Y, et al. The effect of deacetylated gellan gum on aesculin distribution in the posterior segment of the eye after topical administration. Drug Deliv, 2012, 19(4): 194-201.DOI: 10.3109/10717544.2012.690003.
|
[7] |
Campbell RJ, Gill SS, Bronskill SE, et al. Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study. BMJ, 2012, 37(9): 723-733.DOI: 10.1136/bmj.e4203.
|
[8] |
Goldberg RA, Flynn HW Jr, Isom RF, et al. An outbreak of streptococcus endophthalmitis after intravitreal injection of
|
|
bevacizumab. Am J Ophthalmol, 2012, 153(2): 204-208. DOI:10.1016/j.ajo.2011.11.035.
|
[9] |
Cheng L, Hostetler KY, Lee J, et al. Characterization of a novel intraocular drug delivery system using crystalline lipid antiviral prodrugs of ganciclovir and cyclic cidofovir. Invest Ophthalmol Vis Sci, 2004, 45(11): 4138-4144. DOI: 10.1167/iovs.04-0064.
|
[10] |
Cheung CS, Wong AW, Lui A, et al. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections.Ophthalmology, 2012, 119(8): 1609-1614. DOI: 10.1016/j.ophtha.2012.02.014.
|
[11] |
Kompella UB, Bandi N, Ayalasomayajula SP. Subconjunctival nano- and microparticles sustain retinal delivery of budesonide,a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci, 2003, 44(3): 1192-1201. DOI: 10.1167/iovs.02-0791.
|
[8] |
Goldberg RA, Flynn HW Jr, Isom RF, et al. An outbreak of streptococcus endophthalmitis after intravitreal injection of
|
|
bevacizumab. Am J Ophthalmol, 2012, 153(2): 204-208. DOI:10.1016/j.ajo.2011.11.035.
|
[9] |
Cheng L, Hostetler KY, Lee J, et al. Characterization of a novel intraocular drug delivery system using crystalline lipid antiviral prodrugs of ganciclovir and cyclic cidofovir. Invest Ophthalmol Vis Sci, 2004, 45(11): 4138-4144. DOI: 10.1167/iovs.04-0064.
|
[10] |
Cheung CS, Wong AW, Lui A, et al. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections.Ophthalmology, 2012, 119(8): 1609-1614. DOI: 10.1016/j.ophtha.2012.02.014.
|
[11] |
Kompella UB, Bandi N, Ayalasomayajula SP. Subconjunctival nano- and microparticles sustain retinal delivery of budesonide,a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci, 2003, 44(3): 1192-1201. DOI: 10.1167/iovs.02-0791.
|
[12] |
Giordano GG, Refojo MF, Arroyo MH. Sustained delivery of retinoic acid from microspheres of biodegradable polymer in
|
[12] |
Giordano GG, Refojo MF, Arroyo MH. Sustained delivery of retinoic acid from microspheres of biodegradable polymer in
|
|
PVR. Invest Ophthalmol Vis Sci, 1993, 34(9): 2743-2751.
|
|
PVR. Invest Ophthalmol Vis Sci, 1993, 34(9): 2743-2751.
|
[13] |
Kimura H, Ogura Y, Moritera T, et al. Injectable microspheres with controlled drug release for glaucoma filtering surgery.Invest Ophthalmol Vis Sci, 1992, 33(12): 3436-3441.
|
[14] |
del Pozo-Rodríguez A, Delgado D, Gascón AR, et al. Lipid nanoparticles as drug/gene delivery systems to the retina. J Ocul Pharmacol Ther, 2013, 29(2): 173-188. DOI: 10.1089/jop.2012.0128.
|
[15] |
Hayden BC, Jockovich ME, Murray TG, et al. Pharmacokinetics of systemic versus focal Carboplatin chemotherapy in the rabbit eye: possible implication in the treatment of retinoblastoma.Invest Ophthalmol Vis Sci, 2004, 45(10): 3644-3649. DOI: 10.1167/iovs.04-0228.
|
[16] |
Olsen TW, Aaberg SY, Geroski DH, et al. Human sclera:thickness and surface area. Am J Ophthalmol, 1998, 125(2): 237-241. DOI: 10.1016/s0002-9394(99)80096-8.
|
[17] |
Tratta E, Pescina S, Padula C, et al. In vitro permeability of a model protein across ocular tissues and effect of iontophoresis on the transscleral delivery. Eur J Pharm Biopharm, 2014, 88(1):116-122. DOI: 10.1016/j.ejpb.2014.04.018.
|
[13] |
Kimura H, Ogura Y, Moritera T, et al. Injectable microspheres with controlled drug release for glaucoma filtering surgery.Invest Ophthalmol Vis Sci, 1992, 33(12): 3436-3441.
|
[14] |
del Pozo-Rodríguez A, Delgado D, Gascón AR, et al. Lipid nanoparticles as drug/gene delivery systems to the retina. J Ocul Pharmacol Ther, 2013, 29(2): 173-188. DOI: 10.1089/jop.2012.0128.
|
[15] |
Hayden BC, Jockovich ME, Murray TG, et al. Pharmacokinetics of systemic versus focal Carboplatin chemotherapy in the rabbit eye: possible implication in the treatment of retinoblastoma.Invest Ophthalmol Vis Sci, 2004, 45(10): 3644-3649. DOI: 10.1167/iovs.04-0228.
|
[16] |
Olsen TW, Aaberg SY, Geroski DH, et al. Human sclera:thickness and surface area. Am J Ophthalmol, 1998, 125(2): 237-241. DOI: 10.1016/s0002-9394(99)80096-8.
|
[17] |
Tratta E, Pescina S, Padula C, et al. In vitro permeability of a model protein across ocular tissues and effect of iontophoresis on the transscleral delivery. Eur J Pharm Biopharm, 2014, 88(1):116-122. DOI: 10.1016/j.ejpb.2014.04.018.
|
[18] |
Huang D, Wang L, Dong Y, et al. A novel technology using
|
[18] |
Huang D, Wang L, Dong Y, et al. A novel technology using
|
|
transscleral ultrasound to deliver protein loaded nanoparticles.
|
|
Eur J Pharm Biopharm, 2014, 88(1): 104-115. DOI: 10.1016/j.ejpb.2014.04.011.
|
|
transscleral ultrasound to deliver protein loaded nanoparticles.
|
|
Eur J Pharm Biopharm, 2014, 88(1): 104-115. DOI: 10.1016/j.ejpb.2014.04.011.
|
[19] |
Ambati J, Canakis CS, Miller JW, et al. Diffusion of high molecular weight compounds through sclera. Invest Ophthalmol Vis Sci, 2000, 41(5): 1181-1185.
|
[20] |
Shen L, You Y, Sun S, et al. Intraocular and systemic pharmacokinetics of triamcinolone acetonide after a single 40-mg posterior subtenon application. Ophthalmology, 2010,117(12): 2365-2371. DOI: 10.1016/j.ophtha.2010.03.033.
|
[19] |
Ambati J, Canakis CS, Miller JW, et al. Diffusion of high molecular weight compounds through sclera. Invest Ophthalmol Vis Sci, 2000, 41(5): 1181-1185.
|
[20] |
Shen L, You Y, Sun S, et al. Intraocular and systemic pharmacokinetics of triamcinolone acetonide after a single 40-mg posterior subtenon application. Ophthalmology, 2010,117(12): 2365-2371. DOI: 10.1016/j.ophtha.2010.03.033.
|
[21] |
Nan K, Sun S, Li Y, et al. Characterisation of systemic and
|
|
ocular drug level of triamcinolone acetonide following a single sub-Tenon injection. Br J Ophthalmol, 2010, 94(5): 654-658.DOI: 10.1136/bjo.2009.172106.
|
[21] |
Nan K, Sun S, Li Y, et al. Characterisation of systemic and
|
|
ocular drug level of triamcinolone acetonide following a single sub-Tenon injection. Br J Ophthalmol, 2010, 94(5): 654-658.DOI: 10.1136/bjo.2009.172106.
|
[22] |
Silva PS, Singh RJ, Bakri SJ, et al. Vitreous concentration
|
|
of triamcinolone acetonide after a single transseptal depot injection. Ocul Immunol Inflamm, 2009, 17(3): 216-220. DOI:10.1080/09273940802687838.
|
[23] |
Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv, 2004, 1(1): 99-114. DOI: 10.1517/17425247.1.1.99.
|
[24] |
Yoshida J, Wicks RT, Zambrano AI, et al. Inhibition of corneal neovascularization by subconjunctival injection of fc-endostatin,a novel inhibitor of angiogenesis. J Ophthalmol, 2015, 2015:137136. DOI: 10.1155/2015/137136.
|
[22] |
Silva PS, Singh RJ, Bakri SJ, et al. Vitreous concentration
|
|
of triamcinolone acetonide after a single transseptal depot injection. Ocul Immunol Inflamm, 2009, 17(3): 216-220. DOI:10.1080/09273940802687838.
|
[23] |
Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv, 2004, 1(1): 99-114. DOI: 10.1517/17425247.1.1.99.
|
[24] |
Yoshida J, Wicks RT, Zambrano AI, et al. Inhibition of corneal neovascularization by subconjunctival injection of fc-endostatin,a novel inhibitor of angiogenesis. J Ophthalmol, 2015, 2015:137136. DOI: 10.1155/2015/137136.
|
[25] |
El Zaoui I, Touchard E, Berdugo M, et al. Subconjunctival
|
|
Injection of XG-102, a c-Jun N-Terminal Kinase Inhibitor Peptide, in the Treatment of Endotoxin-Induced Uveitis in Rats.J Ocul Pharmacol Ther, 2014, 31(1): 17-24. DOI: 10.1089/jop.2014.0019.
|
[25] |
El Zaoui I, Touchard E, Berdugo M, et al. Subconjunctival
|
|
Injection of XG-102, a c-Jun N-Terminal Kinase Inhibitor Peptide, in the Treatment of Endotoxin-Induced Uveitis in Rats.J Ocul Pharmacol Ther, 2014, 31(1): 17-24. DOI: 10.1089/jop.2014.0019.
|
[26] |
Wu ZH, Feng CX, Tian J, et al. Study on the inhibitory effect of avastin by subconjunctival injection on corneal neovascularization and its mechanisms. International Eye Science, 2013, 13: 52-55.
|
[26] |
Wu ZH, Feng CX, Tian J, et al. Study on the inhibitory effect of avastin by subconjunctival injection on corneal neovascularization and its mechanisms. International Eye Science, 2013, 13: 52-55.
|
[27] |
Chong RS, Su DH, Tsai A, et al. Patient acceptance and attitude
|
|
toward an alternative method of subconjunctival injection for the medical treatment of glaucoma. J Glaucoma, 2013, 22(3):190-194. DOI: 10.1097/ijg.0b013e318237c6c4.
|
[27] |
Chong RS, Su DH, Tsai A, et al. Patient acceptance and attitude
|
|
toward an alternative method of subconjunctival injection for the medical treatment of glaucoma. J Glaucoma, 2013, 22(3):190-194. DOI: 10.1097/ijg.0b013e318237c6c4.
|
[28] |
Albini TA, Zamir E, Read RW, et al. Evaluation of
|
|
Subconjunctival Triamcinolone for Nonnecrotizing Anterior Scleritis. Ophthalmology, 2005, 112(10): 1814-1820. DOI:10.1016/j.ophtha.2005.05.008.
|
[28] |
Albini TA, Zamir E, Read RW, et al. Evaluation of
|
|
Subconjunctival Triamcinolone for Nonnecrotizing Anterior Scleritis. Ophthalmology, 2005, 112(10): 1814-1820. DOI:10.1016/j.ophtha.2005.05.008.
|
[29] |
Stein R, Romano A, Treister G, et al. Effect of subconjunctival injection of hyaluronidase on outflow resistance in normal and in open-angle glaucomatous patients. Metab Pediatr Syst Ophthalmol, 1982, 6(3-4): 169-174.
|
[30] |
Chong YJ, Wong CK, Ismail S. Conjunctival necrosis following a subconjunctival injection of triamcinolone acetonide in a child. Middle East Afr J Ophthalmol, 2015, 22(1): 125-128. DOI:10.4103/0974-9233.148364.
|
[29] |
Stein R, Romano A, Treister G, et al. Effect of subconjunctival injection of hyaluronidase on outflow resistance in normal and in open-angle glaucomatous patients. Metab Pediatr Syst Ophthalmol, 1982, 6(3-4): 169-174.
|
[30] |
Chong YJ, Wong CK, Ismail S. Conjunctival necrosis following a subconjunctival injection of triamcinolone acetonide in a child. Middle East Afr J Ophthalmol, 2015, 22(1): 125-128. DOI:10.4103/0974-9233.148364.
|
[31] |
Güngor IU, Beden U, Erkan D. Conjunctival necrosis due to subconjunctival injection of betamethasone in treatment of graft rejection after penetrating keratoplasty. Ophthalmic Surg Lasers Imaging, 2005, 36(4): 348-349.
|
[31] |
Güngor IU, Beden U, Erkan D. Conjunctival necrosis due to subconjunctival injection of betamethasone in treatment of graft rejection after penetrating keratoplasty. Ophthalmic Surg Lasers Imaging, 2005, 36(4): 348-349.
|
[32] |
Zamir E, Pe'er J. Necrotizing conjunctival ulceration following subconjunctival depot methylprednisolone injection. Ophthalmic Surg Lasers, 1999, 30(7): 565-566.
|
[33] |
Thakur A, Kadam RS, Kompella UB. Influence of drug solubility and lipophilicity on transscleral retinal delivery of six corticosteroids. Drug Metab Dispos, 2011, 39(5): 771-781. DOI:10.1124/dmd.110.037408.
|
[34] |
Resende AP, São Braz B, Delgado E. Ocular Erythropoietin Penetration after Subconjunctival Administration in Glaucomatous Rats. Ophthalmic Res, 2016, 56(2): 104-110.DOI: 10.1159/000444327.
|
[32] |
Zamir E, Pe'er J. Necrotizing conjunctival ulceration following subconjunctival depot methylprednisolone injection. Ophthalmic Surg Lasers, 1999, 30(7): 565-566.
|
[33] |
Thakur A, Kadam RS, Kompella UB. Influence of drug solubility and lipophilicity on transscleral retinal delivery of six corticosteroids. Drug Metab Dispos, 2011, 39(5): 771-781. DOI:10.1124/dmd.110.037408.
|
[34] |
Resende AP, São Braz B, Delgado E. Ocular Erythropoietin Penetration after Subconjunctival Administration in Glaucomatous Rats. Ophthalmic Res, 2016, 56(2): 104-110.DOI: 10.1159/000444327.
|
[35] |
Lin D, Yang YZ, Duan YQ, et al. Pharmacokinetic study of vitreous and aqueous humors concentrations of demethylvancomycin after subconjunctival injection and posterior sub-tenon's continuous infusion with a micro pump in vivo. Invest Ophthalmol Vis Sci, 2016, 57(12): 6414-6414.
|
[36] |
Kim ES, Durairaj C, Kadam RS, et al. Human Scleral Diffusion of Anticancer Drugs from Solution and Nanoparticle Formulation. Pharm Res, 2009, 26(5): 1155-1161. DOI: 10.1007/s11095-009-9835-0.
|
[37] |
Andhariya JV, Burgess DJ. Recent advances in testing of microsphere drug delivery systems. Expert Opin Drug Deliv,2016, 13(4): 593-608. DOI: 10.1517/17425247.2016.1134484.
|
[38] |
de Rojas Silva MV, Rodríguez-Ares MT, Sánchez-Salorio M, et al.Efficacy of subconjunctival cyclosporin-containing microspheres on keratoplasty rejection in the rabbit. Graefes Arch Clin Exp Ophthalmol, 1999, 237(10): 840-847. DOI:10.1007/s004170050321.
|
[39] |
Shive MS, Anderson JM. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev, 1997, 28(1): 5-24. DOI: 10.1016/j.addr.2012.09.004.
|
[40] |
Cui LJ, Sun NX, Li XH, et al. Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery. Acta Pharmacol Sin, 2008, 29(9): 1021-1028. DOI: 10.1111/j.1745-7254.2008.00833.x.
|
[41] |
Ayalasomayajula SP, Kompella UB. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol, 2005, 511(2-3): 191-198. DOI:10.1016/j.ejphar.2005.02.019.
|
[35] |
Lin D, Yang YZ, Duan YQ, et al. Pharmacokinetic study of vitreous and aqueous humors concentrations of demethylvancomycin after subconjunctival injection and posterior sub-tenon's continuous infusion with a micro pump in vivo. Invest Ophthalmol Vis Sci, 2016, 57(12): 6414-6414.
|
[36] |
Kim ES, Durairaj C, Kadam RS, et al. Human Scleral Diffusion of Anticancer Drugs from Solution and Nanoparticle Formulation. Pharm Res, 2009, 26(5): 1155-1161. DOI: 10.1007/s11095-009-9835-0.
|
[37] |
Andhariya JV, Burgess DJ. Recent advances in testing of microsphere drug delivery systems. Expert Opin Drug Deliv,2016, 13(4): 593-608. DOI: 10.1517/17425247.2016.1134484.
|
[38] |
de Rojas Silva MV, Rodríguez-Ares MT, Sánchez-Salorio M, et al.Efficacy of subconjunctival cyclosporin-containing microspheres on keratoplasty rejection in the rabbit. Graefes Arch Clin Exp Ophthalmol, 1999, 237(10): 840-847. DOI:10.1007/s004170050321.
|
[39] |
Shive MS, Anderson JM. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev, 1997, 28(1): 5-24. DOI: 10.1016/j.addr.2012.09.004.
|
[40] |
Cui LJ, Sun NX, Li XH, et al. Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery. Acta Pharmacol Sin, 2008, 29(9): 1021-1028. DOI: 10.1111/j.1745-7254.2008.00833.x.
|
[41] |
Ayalasomayajula SP, Kompella UB. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol, 2005, 511(2-3): 191-198. DOI:10.1016/j.ejphar.2005.02.019.
|
[42] |
Saishin Y, Silva RL, Saishin Y, et al. Periocular injection of microspheres containing PKC412 inhibits choroidal
|
|
neovascularization in a porcine model. Invest Ophthalmol Vis Sci, 2003, 44(11): 4989-4993. DOI: 10.1167/iovs.03-0600.
|
[43] |
Carrasquillo KG, Ricker JA, Rigas IK, et al. Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic) acid microspheres. Invest Ophthalmol Vis Sci, 2003, 44(1): 290-299. DOI: 10.1167/iovs.01-1156.
|
[44] |
Cellini M, Pazzaglia A, Zamparini E, et al. Intravitreal vs. subtenon triamcinolone acetonide for the treatment of diabetic cystoid macular edema. BMC Ophthalmol, 2008, 8:5. DOI: 10.1186/1471-2415-8-5.
|
[45] |
Lam DS, Chan CK, Mohamed S, et al. A prospective randomised trial of different doses of intravitreal triamcinolone for diabetic macular oedema. Br J Ophthalmol, 2007, 91(2): 199-203. DOI:10.1136/bjo.2006.102848.
|
[42] |
Saishin Y, Silva RL, Saishin Y, et al. Periocular injection of microspheres containing PKC412 inhibits choroidal
|
|
neovascularization in a porcine model. Invest Ophthalmol Vis Sci, 2003, 44(11): 4989-4993. DOI: 10.1167/iovs.03-0600.
|
[43] |
Carrasquillo KG, Ricker JA, Rigas IK, et al. Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic) acid microspheres. Invest Ophthalmol Vis Sci, 2003, 44(1): 290-299. DOI: 10.1167/iovs.01-1156.
|
[44] |
Cellini M, Pazzaglia A, Zamparini E, et al. Intravitreal vs. subtenon triamcinolone acetonide for the treatment of diabetic cystoid macular edema. BMC Ophthalmol, 2008, 8:5. DOI: 10.1186/1471-2415-8-5.
|
[45] |
Lam DS, Chan CK, Mohamed S, et al. A prospective randomised trial of different doses of intravitreal triamcinolone for diabetic macular oedema. Br J Ophthalmol, 2007, 91(2): 199-203. DOI:10.1136/bjo.2006.102848.
|
[46] |
Jonas JB, Spandau UH, Kamppeter BA, et al. Duration of the effect of intravitreal triamcinolone acetonide in eyes with
|
|
exudative age-related macular degeneration. J Ocul Pharmacol Ther, 2006, 22(3): 194-199. DOI: 10.1089/jop.2006.22.194.
|
[47] |
Kadam RS, Tyagi P, Edelhauser HF, et al. Influence of choroidal neovascularization and biodegradable polymeric particle size on transscleral sustained delivery of triamcinolone acetonide.Int J Pharm, 2012, 434(1): 140-147. DOI: 10.1016/j.ijpharm.2012.05.025.
|
[48] |
Amrite AC, Kompella UB. Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration. J Pharm Pharmacol, 2005, 57(12): 1555-1563.DOI: 10.1211/jpp.57.12.0005.
|
[46] |
Jonas JB, Spandau UH, Kamppeter BA, et al. Duration of the effect of intravitreal triamcinolone acetonide in eyes with
|
|
exudative age-related macular degeneration. J Ocul Pharmacol Ther, 2006, 22(3): 194-199. DOI: 10.1089/jop.2006.22.194.
|
[47] |
Kadam RS, Tyagi P, Edelhauser HF, et al. Influence of choroidal neovascularization and biodegradable polymeric particle size on transscleral sustained delivery of triamcinolone acetonide.Int J Pharm, 2012, 434(1): 140-147. DOI: 10.1016/j.ijpharm.2012.05.025.
|
[48] |
Amrite AC, Kompella UB. Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration. J Pharm Pharmacol, 2005, 57(12): 1555-1563.DOI: 10.1211/jpp.57.12.0005.
|
[49] |
Amrite AC, Edelhauser HF, Singh SR, et al. Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration. Mol Vis, 2008, 14:150-160.
|
[49] |
Amrite AC, Edelhauser HF, Singh SR, et al. Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration. Mol Vis, 2008, 14:150-160.
|
[50] |
Gu B, Li X, Liu j, et al. Determination of the effect size of conjunctival and episcleral circulation on transscleral drug delivery. IOVS, 2016: abstract#3456.
|
[51] |
Liu X, Li Y, Zhang Y, et al. Comparison of intraocular pressure elevation after anterior versus posterior subtenon triamcinolone acetonide acetate injection: a retrospective study. Reina, 2012,32(9): 1838-1843. DOI: 10.1097/IAE.0b013e31824fd384.
|
[52] |
Sun S, Li J, Li X, et al. Episcleral drug film for better-targeted ocular drug delivery and controlled release using multilayered poly-ε-caprolactone (PCL). Acta Biomater, 2016, 37: 143-154.DOI: 10.1016/j.actbio.2016.04.014.
|
[53] |
Chen M, Li X, Liu J, et al. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model. J Control Release, 2015,203:109-117. DOI: 10.1016/j.jconrel.2015.02.021.
|
[54] |
Meng Y, Sun S, Li J, et al. Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-ε-caprolactone matrix. Acta Biomater, 2014, 10(1): 126-133. DOI: 10.1016/j.actbio.2013.09.022.
|
[55] |
Peng Y, Ang M, Foo S, et al. Biocompatibility and biodegradation studies of subconjunctival implants in rabbit eyes. PloS One,2011, 6(7): e22507. DOI: 10.1371/journal.pone.0022507.
|
[56] |
Gilger BC, Salmon JH, Wilkie DA, et al. A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. Invest Ophthalmol Vis Sci, 2006, 47(6): 2596-2605. DOI: 10.1167/iovs.05-1540.
|
[50] |
Gu B, Li X, Liu j, et al. Determination of the effect size of conjunctival and episcleral circulation on transscleral drug delivery. IOVS, 2016: abstract#3456.
|
[51] |
Liu X, Li Y, Zhang Y, et al. Comparison of intraocular pressure elevation after anterior versus posterior subtenon triamcinolone acetonide acetate injection: a retrospective study. Reina, 2012,32(9): 1838-1843. DOI: 10.1097/IAE.0b013e31824fd384.
|
[52] |
Sun S, Li J, Li X, et al. Episcleral drug film for better-targeted ocular drug delivery and controlled release using multilayered poly-ε-caprolactone (PCL). Acta Biomater, 2016, 37: 143-154.DOI: 10.1016/j.actbio.2016.04.014.
|
[53] |
Chen M, Li X, Liu J, et al. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model. J Control Release, 2015,203:109-117. DOI: 10.1016/j.jconrel.2015.02.021.
|
[54] |
Meng Y, Sun S, Li J, et al. Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-ε-caprolactone matrix. Acta Biomater, 2014, 10(1): 126-133. DOI: 10.1016/j.actbio.2013.09.022.
|
[55] |
Peng Y, Ang M, Foo S, et al. Biocompatibility and biodegradation studies of subconjunctival implants in rabbit eyes. PloS One,2011, 6(7): e22507. DOI: 10.1371/journal.pone.0022507.
|
[56] |
Gilger BC, Salmon JH, Wilkie DA, et al. A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. Invest Ophthalmol Vis Sci, 2006, 47(6): 2596-2605. DOI: 10.1167/iovs.05-1540.
|
|
|
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