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Review

Recent perspectives on the delivery of biologics to back of the eye

, , , &
Pages 631-645 | Received 26 May 2016, Accepted 17 Aug 2016, Published online: 06 Sep 2016

References

  • The global economic cost of visual impairment; 2014. Available from: http://www.icoph.org/resources/146/The-Global-Economic-Cost-of-Visual-Impairment.html
  • 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.
  • Gaudana R, Ananthula HK, Parenky A, et al. Ocular drug delivery. AAPS J. 2010;12(3):348–360.
  • Zajac-Pytrus HM, Pilecka A, Turno-Krecicka A, et al. The dry form of age-related macular degeneration (amd): the current concepts of pathogenesis and prospects for treatment. Adv Clin Exp Med Off Organ Wroclaw Med Univ. 2015;24(6):1099–1104.
  • Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vision. 2015;2:17.
  • Wiersbitzky S, Ballke EH, Burghardt R, et al. long-term study of various immunologic functions in children with chronic nonspecific lung diseases. Z Erkr Atmungsorgane. 1985;164(3):241–253.
  • Mohamed R, El-Remessy AB. Imbalance of the nerve growth factor and its precursor: implication in diabetic retinopathy. J Clin Exp Ophthalmol. 2015;6:5.
  • Fogli S, Mogavero S, Egan CG, et al. Pathophysiology and pharmacological targets of vegf in diabetic macular edema. Pharmacol Res. 2016;103:149–157.
  • Takeuchi M. A systematic review of biologics for the treatment of noninfectious uveitis. Immuno Ther. 2013;5(1):91–102.
  • Posarelli C, Arapi I, Figus M, et al. Biologic agents in inflammatory eye disease. J Ophthalmic Vis Res. 2011;6(4):309–316. .
  • McKibbin M, Devonport H, Gale R, et al. Aflibercept in wet amd beyond the first year of treatment: recommendations by an expert roundtable panel. Eye. 2015;29(Suppl 1):S1–S11.
  • Heier JS, Bressler NM, Avery RL, et al. Comparison of aflibercept, bevacizumab, and ranibizumab for treatment of diabetic macular edema: extrapolation of data to clinical practice. JAMA Ophthalmol. 2016;134(1):95–99.
  • Bressler NM, Varma R, Mitchell P, et al. Effect of ranibizumab on the decision to drive and vision function relevant to driving in patients with diabetic macular edema: report from restore, ride, and rise trials. JAMA Ophthalmol. 2016;134(2):160–166.
  • Gibson JM, McGinnigle S. Diabetes: intravitreous ranibizumab for proliferative diabetic retinopathy. Nat Rev Endocrinol. 2016;12(3):130–131.
  • Rush RB, Rush SW. Ranibizumab versus bevacizumab for neovascular age-related macular degeneration with an incomplete posterior vitreous detachment. Asia-Pacific J Ophthalmol. 2016;5(3):171–175.
  • Chin-Yee D, Eck T, Fowler S, et al. A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration. Br J Ophthalmol. 2016;100:914–917.
  • Amadio M, Govoni S, Pascale A. Targeting vegf in eye neovascularization: What’s new? A comprehensive review on current therapies and oligonucleotide-based interventions under development. Pharmacol Res. 2016;103:253–269.
  • Ho M, Liu DT, Lam DS, et al. Retinal vein occlusions, from basics to the latest treatment. Retina. 2016;36(3):432–448.
  • Cholkar K, Patel A, Vadlapudi AD, et al. Novel nanomicellar formulation approaches for anterior and posterior segment ocular drug delivery. Recent Pat Nanomed. 2012;2(2):82–95.
  • Vaishya RD, Mandal A, Patel S, et al. Extended release microparticle-in-gel formulation of octreotide: effect of polymer type on acylation of peptide during in vitro release. Int J Pharm. 2015;496(2):676–688.
  • Vaishya RD, Mandal A, Gokulgandhi M, et al. Reversible hydrophobic ion-paring complex strategy to minimize acylation of octreotide during long-term delivery from plga microparticles. Int J Pharm. 2015;489(1–2):237–245.
  • Comparison of Age-related Macular Degeneration Treatments Trials Research G, Maguire MG, Martin DF, et al. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2016;123(8):1751–1761.
  • Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase iii randomized trials: rise and ride. Ophthalmology. 2012;119(4):789–801.
  • Jackson TL, Desai R, Simpson A, et al. Epimacular brachytherapy for previously treated neovascular age-related macular degeneration (merlot): a phase 3 randomized controlled trial. Ophthalmology. 2016;123:1287–1296.
  • Tadayoni R, Waldstein SM, Boscia F, et al. Individualized stabilization criteria-driven ranibizumab versus laser in branch retinal vein occlusion: six-month results of brighter. Ophthalmology. 2016;123:1332–1344.
  • Pfau M, Fassnacht-Riederle HM, Freiberg FJ, et al. switching therapy from ranibizumab and/or bevacizumab to aflibercept in neovascular age-related macular degeneration (amd): one-year results. Klin Monbl Augenheilkd. 2016;233(8):945–950.
  • Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121(11):2247–2254.
  • Sivaprasad S, Prevost AT, Bainbridge J, et al. Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (acronym clarity): a multicentre phase iib randomised active-controlled clinical trial. BMJ Open. 2015;5(9):e008405.
  • Comparison of Age-related Macular Degeneration Treatments Trials Research G, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119(7):1388–1398.
  • Shiragami C, Ono A, Kobayashi M, et al. Effect of switching therapy to pegaptanib in eyes with the persistent cases of exudative age-related macular degeneration. Medicine. 2014;93(18):e116.
  • Good TJ, Kimura AE, Mandava N, et al. Sustained elevation of intraocular pressure after intravitreal injections of anti-vegf agents. Br J Ophthalmol. 2011;95(8):1111–1114.
  • Hoang QV, Tsuang AJ, Gelman R, et al. Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy. Retina. 2013;33(1):179–187.
  • Yu AL, Seidensticker F, Schaumberger M, et al. Evaluation of intraocular pressure elevation after multiple injections of intravitreal ranibizumab. Clin Ophthalmol. 2014;8:743–747.
  • Patel SP, Vaishya R, Pal D, et al. Novel pentablock copolymer-based nanoparticulate systems for sustained protein delivery. AAPS Pharm Sci Tech. 2015;16(2):327–343.
  • Ozaki T, Nakazawa M, Yamashita T, et al. Delivery of topically applied calpain inhibitory peptide to the posterior segment of the rat eye. PLoS One. 2015;10(6):e0130986.
  • Schopf LR, Popov AM, Enlow EM, et al. Topical ocular drug delivery to the back of the eye by mucus-penetrating particles. Transl Vis Sci Technol. 2015;4(3):11.
  • Cholkar K, Gilger BC, Mitra AK. Topical, aqueous, clear cyclosporine formulation design for anterior and posterior ocular delivery. Transl Vis Sci Technol. 2015;4(3):1. .
  • Moisseiev E, Waisbourd M, Ben-Artsi E, et al. Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes. Graefe’s Archive for Clin and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2014;252(2):331–337.
  • Davis BM, Normando EM, Guo L, et al. Topical delivery of avastin to the posterior segment of the eye in vivo using annexin a5-associated liposomes. Small. 2014;10(8):1575–1584.
  • Chen JJ, Ebmeier SE, Sutherland WM, et al. Potential penetration of topical ranibizumab (lucentis) in the rabbit eye. Eye. 2011;25(11):1504–1511.
  • Ford KM, Saint-Geniez M, Walshe TE, et al. Expression and role of vegf–a in the ciliary body. Invest Ophthalmol Vis Sci. 2012;53(12):7520–7527.
  • Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003;26(9):2653–2664.
  • Shah CA. Diabetic retinopathy: a comprehensive review. Indian J Med Sci. 2008;62(12):500–519.
  • Simo R, Carrasco E, Garcia-Ramirez M, et al. Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev. 2006;2(1):71–98.
  • Rotsos TG, Moschos MM. Cystoid macular edema. Clin Ophthalmol. 2008;2(4):919–930.
  • Marashi A. Using anti-vegf in diabetic retinopathy. Adv Ophthalmol Vis Syst. 2016;4:4.
  • Crawford TN, Alfaro DV III, Kerrison JB, et al. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev. 2009;5(1):8–13.
  • Gupta N, Mansoor S, Sharma A, et al. Diabetic retinopathy and vegf. Open Ophthalmol J. 2013;7:4–10.
  • Kim JH, Kim JH, Yu YS, et al. Blockade of angiotensin ii attenuates vegf-mediated blood-retinal barrier breakdown in diabetic retinopathy. J Cereb Blood Flow Metab. 2009;29(3):621–628.
  • Wang Y, Yan H. Microrna-126 contributes to niaspan treatment induced vascular restoration after diabetic retinopathy. Sci Rep. 2016;6:26909.
  • Nowak JZ. Age-related macular degeneration (amd): pathogenesis and therapy. Pharmacol Rep. 2006;58(3):353–363.
  • Chappelow AV, Kaiser PK. Neovascular age-related macular degeneration: potential therapies. Drugs. 2008;68(8):1029–1036.
  • Green WR, McDonnell PJ, Yeo JH. Pathologic features of senile macular degeneration. 1985. Retina. 2005;25(5 Suppl):615–627.
  • Bressler SB, Silva JC, Bressler NM, et al. Clinicopathologic correlation of occult choroidal neovascularization in age-related macular degeneration. 1992. Retina. 2005;25(5 Suppl):827–832.
  • Agarwal A, Rhoades WR, Hanout M, et al. Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development. Clin Ophthalmology. 2015;9:1001–1015.
  • Pastor JC. Proliferative vitreoretinopathy: an overview. Surv Ophthalmol. 1998;43(1):3–18.
  • Kon CH, Asaria RH, Occleston NL, et al. Risk factors for proliferative vitreoretinopathy after primary vitrectomy: a prospective study. Br J Ophthalmol. 2000;84(5):506–511.
  • Sadaka A, Giuliari GP. Proliferative vitreoretinopathy: current and emerging treatments. Clin Ophthalmol. 2012;6:1325–1333.
  • Kwon OW, Roh MI, Song JH. Retinal detachment and proliferative vitreoretinopathy. In: Retinal diseases amenable to pharmacotherapy. Dev Ophthalmol. 2016;55;154–162.
  • Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv Ophthalmol. 2000;44(5):367–408.
  • Yi X, Wang Y, Yu FS. Corneal epithelial tight junctions and their response to lipopolysaccharide challenge. Invest Ophthalmol Vis Sci. 2000;41(13):4093–4100.
  • Mitic LL, Van Itallie CM, Anderson JM. Molecular physiology and pathophysiology of tight junctions i. Tight junction structure and function: lessons from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol. 2000;279(2):G250–254.
  • Edward A, Prausnitz MR. Predicted permeability of the cornea to topical drugs. Pharm Res. 2001;18(11):1497–1508.
  • Van Haeringen NJ, Glasius E. Lysosomal hydrolases in tears and the lacrimal gland: effect of acetylsalicylic acid on the release from the lacrimal gland. Invest Ophthalmol Vis Sci. 1980;19(7):826–829.
  • Huang AJ, Tseng SC, Kenyon KR. Paracellular permeability of corneal and conjunctival epithelia. Invest Ophthalmol Vis Sci. 1989;30(4):684–689.
  • Kim SH, Galban CJ, Lutz RJ, et al. Assessment of subconjunctival and intrascleral drug delivery to the posterior segment using dynamic contrast-enhanced magnetic resonance imaging. Invest Ophthalmol Vis Sci. 2007;48(2):808–814.
  • Nakao S, Hafezi-Moghadam A, Ishibashi T. Lymphatics and lymphangiogenesis in the eye. J Ophthalmol. 2012;2012:1–11.
  • Bellhorn RW. Permeability of blood-ocular barriers of neonatal and adult cats to fluorescein-labeled dextrans of selected molecular sizes. Invest Ophthalmol Vis Sci. 1981;21(2):282–290.
  • Prausnitz MR, Noonan JS. Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye. J Pharm Sci. 1998;87(12):1479–1488.
  • Olsen TW, Edelhauser HF, Lim JI, et al. Human scleral permeability. Effects of age, cryotherapy, transscleral diode laser, and surgical thinning. Invest Ophthalmol Vis Sci. 1995;36(9):1893–1903.
  • Maurice DM, Polgar J. Diffusion across the sclera. Exp Eye Res. 1977;25(6):577–582.
  • Wen H, Hao J, Li SK. Characterization of human sclera barrier properties for transscleral delivery of bevacizumab and ranibizumab. J Pharm Sci. 2013;102(3):892–903.
  • Pino RM, Essner E. Permeability of rat choriocapillaris to hemeproteins. Restriction of tracers by a fenestrated endothelium. J Histochem Cytochem Off J Histochem Soc. 1981;29(2):281–290.
  • Essner E, Gordon SR. Observations on the permeability of the choriocapillaris of the eye. Cell Tissue Res. 1983;231(3):571–577.
  • Pitkanen L, Ranta VP, Moilanen H, et al. Permeability of retinal pigment epithelium: effects of permeant molecular weight and lipophilicity. Invest Ophthalmol Vis Sci. 2005;46(2):641–646.
  • Jackson TL, Antcliff RJ, Hillenkamp J, et al. Human retinal molecular weight exclusion limit and estimate of species variation. Invest Ophthalmol Vis Sci. 2003;44(5):2141–2146.
  • Tao Y, Li XX, Jiang YR, et al. Diffusion of macromolecule through retina after experimental branch retinal vein occlusion and estimate of intraretinal barrier. Curr Drug Metab. 2007;8(2):151–156.
  • Mordenti J, Cuthbertson RA, Ferrara N, et al. Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125i-labeled full-length and fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol. 1999;27(5):536–544.
  • Tojo K. A pharmacokinetic model for ocular drug delivery. Chem Pharm Bull. 2004;52(11):1290–1294.
  • Bakri SJ, Snyder MR, Reid JM, et al. Pharmacokinetics of intravitreal ranibizumab (lucentis). Ophthalmology. 2007;114(12):2179–2182.
  • Fauser S, Kalbacher H, Alteheld N, et al. Pharmacokinetics and safety of intravitreally delivered etanercept. Graefe’s Archive for Clin and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2004;242(7):582–586.
  • Iyer MN, He F, Wensel TG, et al. Intravitreal clearance of moxifloxacin. Trans Am Ophthalmol Soc. 2005;103:76–81, discussion 81–73.
  • Bakri SJ, Snyder MR, Reid JM, et al. Pharmacokinetics of intravitreal bevacizumab (avastin). Ophthalmology. 2007;114(5):855–859.
  • Xu L, Lu T, Tuomi L, et al. Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach. Invest Ophthalmol Vis Sci. 2013;54(3):1616–1624.
  • Gaudreault J, Fei D, Rusit J, et al. Preclinical pharmacokinetics of ranibizumab (rhufabv2) after a single intravitreal administration. Invest Ophthalmol Vis Sci. 2005;46(2):726–733.
  • Sinapis CI, Routsias JG, Sinapis AI, et al. Pharmacokinetics of intravitreal bevacizumab (avastin(r)) in rabbits. Clin Ophthalmol. 2011;5:697–704.
  • Park SJ, Oh J, Kim YK, et al. Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-trap in a rabbit model. Eye. 2015;29(4):561–568.
  • Miyake T, Sawada O, Kakinoki M, et al. Pharmacokinetics of bevacizumab and its effect on vascular endothelial growth factor after intravitreal injection of bevacizumab in macaque eyes. Invest Ophthalmol Vis Sci. 2010;51(3):1606–1608.
  • Del Amo EM, Urtti A. Rabbit as an animal model for intravitreal pharmacokinetics: clinical predictability and quality of the published data. Exp Eye Res. 2015;137:111–124.
  • Le KN, Gibiansky L, Good J, et al. A mechanistic pharmacokinetic/pharmacodynamic model of factor d inhibition in cynomolgus monkeys by lampalizumab for the treatment of geographic atrophy. J Pharmacol Exp Ther. 2015;355(2):288–296.
  • Drolet DW, Nelson J, Tucker CE, et al. Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (nx1838) following injection into the vitreous humor of rhesus monkeys. Pharm Res. 2000;17(12):1503–1510.
  • Ng EW, Shima DT, Calias P, et al. Pegaptanib, a targeted anti-vegf aptamer for ocular vascular disease. Nat Rev Drug Discovery. 2006;5(2):123–132.
  • Abdelkader H, Alany RG. Controlled and continuous release ocular drug delivery systems: pros and cons. Curr Drug Deliv. 2012;9(4):421–430.
  • Mishra GP, Bagui M, Tamboli V, et al. Recent applications of liposomes in ophthalmic drug delivery. J Drug Deliv. 2011;2011:1–14.
  • Puglia C, Offerta A, Carbone C, et al. Lipid nanocarriers (lnc) and their applications in ocular drug delivery. Curr Med Chem. 2015;22(13):1589–1602.
  • Yellepeddi VK, Palakurthi S. Recent advances in topical ocular drug delivery. J Ocular Pharmacology Therapeutics: Official Journal Assoc Ocul Pharmacol Ther. 2016;32(2):67–82.
  • Hennig R, Goepferich A. Nanoparticles for the treatment of ocular neovascularizations. Eur J Pharmaceutics Biopharm: Official J Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik Ev. 2015;95(Pt B):294–306.
  • Shah SS, Denham LV, Elison JR, et al. Drug delivery to the posterior segment of the eye for pharmacologic therapy. Expert Rev Ophthalmol. 2010;5(1):75–93.
  • Pignatello R, Carbone C, Puglia C, et al. Ophthalmic applications of lipid-based drug nanocarriers: an update of research and patenting activity. Ther Deliv. 2015;6(11):1297–1318.
  • Musumeci T, Bucolo C, Carbone C, et al. Polymeric nanoparticles augment the ocular hypotensive effect of melatonin in rabbits. Int J Pharm. 2013;440(2):135–140.
  • MacDonald IM, Sauve Y, Sieving PA. Preventing blindness in retinal disease: ciliary neurotrophic factor intraocular implants. Can J Ophthalmol J Can D’ophtalmol. 2007;42(3):399–402.
  • Myles ME, Neumann DM, Hill JM. Recent progress in ocular drug delivery for posterior segment disease: emphasis on transscleral iontophoresis. Adv Drug Deliv Rev. 2005;57(14):2063–2079.
  • Hughes PM, Olejnik O, Chang-Lin JE, et al. Topical and systemic drug delivery to the posterior segments. Adv Drug Deliv Rev. 2005;57(14):2010–2032.
  • Marano RJ, Wimmer N, Kearns PS, et al. Inhibition of in vitro vegf expression and choroidal neovascularization by synthetic dendrimer peptide mediated delivery of a sense oligonucleotide. Exp Eye Res. 2004;79(4):525–535.
  • Yasin MN, Svirskis D, Seyfoddin A, et al. Implants for drug delivery to the posterior segment of the eye: a focus on stimuli-responsive and tunable release systems. J Controlled Release Off J Controlled Release Soc. 2014;196:208–221.
  • Rowe-Rendleman CL, Durazo SA, Kompella UB, et al. Drug and gene delivery to the back of the eye: from bench to bedside. Invest Ophthalmol Vis Sci. 2014;55(4):2714–2730.
  • Tucker BA, Mullins RF, Stone EM. Stem cells for investigation and treatment of inherited retinal disease. Hum Mol Genet. 2014;23(R1):R9–R16.
  • Wan C, Li F, Li H. Gene therapy for ocular diseases meditated by ultrasound and microbubbles (review). Mol Med Rep. 2015;12(4):4803–4814.
  • Marchetti V, Krohne TU, Friedlander DF, et al. Stemming vision loss with stem cells. J Clin Invest. 2010;120(9):3012–3021.
  • Vadlapudi AD, Mitra AK. Nanomicelles: an emerging platform for drug delivery to the eye. Ther Deliv. 2013;4(1):1–3.
  • Iriyama A, Oba M, Ishii T, et al. Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo. PLoS One. 2011;6(12):e28560.
  • Ideta R, Yanagi Y, Tamaki Y, et al. Effective accumulation of polyion complex micelle to experimental choroidal neovascularization in rats. FEBS Lett. 2004;557(1–3):21–25.
  • Oh EJ, Choi JS, Kim H, et al. Anti-flt1 peptide - hyaluronate conjugate for the treatment of retinal neovascularization and diabetic retinopathy. Biomaterials. 2011;32(11):3115–3123.
  • Kim H, Choi JS, Kim KS, et al. Flt1 peptide-hyaluronate conjugate micelle-like nanoparticles encapsulating genistein for the treatment of ocular neovascularization. Acta Biomater. 2012;8(11):3932–3940.
  • Ing TS, Yu AW, Thompson KD, et al. Peritoneal dialysis using conventional, lactate–containing solution sterilized by ultrafiltration. Int J Artif Organs. 1992;15(11):658–660.
  • Patel A, Cholkar K, Agrahari V, et al. Ocular drug delivery systems: an overview. World J Pharmacol. 2013;2(2):47–64.
  • Lajavardi L, Bochot A, Camelo S, et al. Downregulation of endotoxin-induced uveitis by intravitreal injection of vasoactive intestinal peptide encapsulated in liposomes. Invest Ophthalmol Vis Sci. 2007;48(7):3230–3238.
  • Lajavardi L, Camelo S, Agnely F, et al. New formulation of vasoactive intestinal peptide using liposomes in hyaluronic acid gel for uveitis. J Controlled Release Off J Controlled Release Soc. 2009;139(1):22–30.
  • Abrishami M, Zarei-Ghanavati S, Soroush D, et al. Preparation, characterization, and in vivo evaluation of nanoliposomes-encapsulated bevacizumab (avastin) for intravitreal administration. Retina. 2009;29(5):699–703.
  • Baranowski P, Karolewicz B, Gajda M, et al. Ophthalmic drug dosage forms: characterisation and research methods. Sci World J. 2014;2014:1–14.
  • Patel SP, Vaishya R, Mishra GP, et al. Tailor-made pentablock copolymer based formulation for sustained ocular delivery of protein therapeutics. J Drug Deliv. 2014;2014:1–15.
  • Sp P, Vaishya R, Yang X, et al. Novel thermosensitive pentablock copolymers for sustained delivery of proteins in the treatment of posterior segment diseases. Protein Pept Lett. 2014;21(11):1185–1200.
  • Yandrapu SK, Upadhyay AK, Petrash JM, et al. Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab. Mol Pharm. 2013;10(12):4676–4686.
  • Feng L, Li SK, Liu H, et al. Ocular delivery of prna nanoparticles: distribution and clearance after subconjunctival injection. Pharm Res. 2014;31(4):1046–1058.
  • Zulliger R, Conley SM, Naash MI. Non-viral therapeutic approaches to ocular diseases: an overview and future directions. J Controlled Release Off J Controlled Release Soc. 2015;219:471–487.
  • Mitra RN, Han Z, Merwin M, et al. Synthesis and characterization of glycol chitosan DNA nanoparticles for retinal gene delivery. ChemMedChem. 2014;9(1):189–196.
  • Koirala A, Conley SM, Makkia R, et al. Persistence of non-viral vector mediated rpe65 expression: case for viability as a gene transfer therapy for rpe-based diseases. J Controlled Release Off J Controlled Release Soc. 2013;172(3):745–752.
  • Ghassemi AH, Van Steenbergen MJ, Barendregt A, et al. Controlled release of octreotide and assessment of peptide acylation from poly(d,l-lactide-co-hydroxymethyl glycolide) compared to plga microspheres. Pharm Res. 2012;29(1):110–120.
  • Shirangi M, Najafi M, Rijkers DT, et al. Inhibition of octreotide acylation inside plga microspheres by derivatization of the amines of the peptide with a self-immolative protecting group. Bioconjug Chem. 2016;27(3):576–585.
  • Wassmer S, Rafat M, Fong WG, et al. Chitosan microparticles for delivery of proteins to the retina. Acta Biomater. 2013;9(8):7855–7864.
  • Panda JJ, Yandrapu S, Kadam RS, et al. Self-assembled phenylalanine-alpha,beta-dehydrophenylalanine nanotubes for sustained intravitreal delivery of a multi-targeted tyrosine kinase inhibitor. J Controlled Release Off J Controlled Release Soc. 2013;172(3):1151–1160.
  • Wang J, Jiang A, Joshi M, et al. Drug delivery implants in the treatment of vitreous inflammation. Mediators Inflamm. 2013;2013:1–8.
  • Sotoodehnejadnematalahi F, Burke B. Human activated macrophages and hypoxia: a comprehensive review of the literature. Iran J Basic Med Sci. 2014;17(11):820–830.
  • Drug delivery to the posterior segment. Available from: http://www.neurotechusa.com/
  • Madaan K, Kumar S, Poonia N, et al. Dendrimers in drug delivery and targeting: drug-dendrimer interactions and toxicity issues. J Pharm Bioallied Sci. 2014;6(3):139–150.
  • Marano RJ, Toth I, Wimmer N, et al. Dendrimer delivery of an anti-vegf oligonucleotide into the eye: a long-term study into inhibition of laser-induced cnv, distribution, uptake and toxicity. Gene Ther. 2005;12(21):1544–1550.
  • Yavuz B, Pehlivan SB, Unlu N. Dendrimeric systems and their applications in ocular drug delivery. Sci World J. 2013;2013:1–13.
  • Jain K, Kesharwani P, Gupta U, et al. Dendrimer toxicity: let’s meet the challenge. Int J Pharm. 2010;394(1–2):122–142.
  • Waite CL, Sparks SM, Uhrich KE, et al. Acetylation of pamam dendrimers for cellular delivery of sirna. BMC Biotechnol. 2009;9:38.
  • Agrawal P, Gupta U, Jain NK. Glycoconjugated peptide dendrimers-based nanoparticulate system for the delivery of chloroquine phosphate. Biomaterials. 2007;28(22):3349–3359.
  • Agashe HB, Dutta T, Garg M, et al. Investigations on the toxicological profile of functionalized fifth-generation poly (propylene imine) dendrimer. J Pharm Pharmacol. 2006;58(11):1491–1498.
  • Stasko NA, Johnson CB, Schoenfisch MH, et al. Cytotoxicity of polypropylenimine dendrimer conjugates on cultured endothelial cells. Biomacromolecules. 2007;8(12):3853–3859.
  • Clinical Trials. Biologic molecules currently in clinical trials for treatment of posterior ocular diseases. Available from: https://clinicaltrials.gov
  • Clinical Trials. A phase 3 safety and efficacy study of Fovista (E10030). Intravenous administration in combination with Lucentis and compared with Lucentis monotherapy [First received September 2013. Last update September 2015]. Clinical Trials Identifier NCT01940900. Available from: https://clinicaltrials.gov/ct2/show/NCT01940900
  • Ishikawa M, Jin D, Sawada Y, et al. Future therapies of wet age-related macular degeneration. J Ophthalmol. 2015;2015:1–10.
  • Ophthotech Corporation. Fovista, anti-PDGF therapy clinical development in combination with anti-VEGF therapy for treatment of wet AMD. Available from: http://www.ophthotech.com/wp-content/uploads/Fovista_Fact_Sheet.pdf
  • Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003;111(9):1287–1295.
  • Dejneka NS, Wan S, Bond OS, et al. Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes. Mol Vis. 2008;14:997–1005.
  • Shen J, Samul R, Silva RL, et al. Suppression of ocular neovascularization with sirna targeting vegf receptor 1. Gene Ther. 2006;13(3):225–234.
  • Kaiser PK, Symons RC, Shah SM, et al. Rnai-based treatment for neovascular age-related macular degeneration by sirna-027. Am J Ophthalmol. 2010;150(1):33–39.e2.
  • Rittenhouse KD, Johnson TR, Vicini P, et al. Rtp801 gene expression is differentially upregulated in retinopathy and is silenced by pf-04523655, a 19-mer sirna directed against rtp801. Invest Ophthalmol Vis Sci. 2014;55(3):1232–1240.
  • Nguyen QD, Schachar RA, Nduaka CI, et al. Phase 1 dose-escalation study of a sirna targeting the rtp801 gene in age-related macular degeneration patients. Eye. 2012;26(8):1099–1105.
  • Atram SC, Bobade NN, Wankhade VP, et al. Current trends towards an ocular drug delivery system. Int J Pharm Pharm Sci Res. 2013;3(1):28–34.
  • Meller D, Thomasen H, Steuhl KP. ocular surface reconstruction in limbal stem cell deficiency: transplantation of cultivated limbal epithelium. Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 2012;109(9):863–868.
  • Basu S, Mohamed A, Chaurasia S, et al. Clinical outcomes of penetrating keratoplasty after autologous cultivated limbal epithelial transplantation for ocular surface burns. Am J Ophthalmol. 2011;152(6):917–924, e911.

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