Nanomedicine-Based Delivery to the Posterior Segment of the Eye: Brighter Tomorrow

  • Afrah Jalil Abd
  • Rupinder Kaur Kanwar
  • Yashwant V. Pathak
  • Maysaa Al Mohammedawi
  • Jagat Rakesh KanwarEmail author


Therapeutic strategies for the posterior ocular segment face tremendous challenges due to the presence of anatomical and physiological ocular barriers. Although several efforts have been conducted to manage the retinal dysfunction via various modes of administration, current therapeutic options have their disadvantages since these routes are invasive and followed by postinjection complications. Due to the possibility of encapsulating medications and to maintain their bioavailability in abundance, nanotechnology has been widely employed in the ophthalmology field particularly to manage disorders regarding the distal point of the eye. In this chapter, we elaborated the concept of using nanoparticles to treat the posterior part of the eye.


Nanomedicine Posterior segment of eye Ocular barriers Drug delivery Retinal diseases 


  1. 1.
    Zarbin MA, Montemagno C, Leary JF, Ritch R. Nanotechnology in ophthalmology. Can J Ophthalmol. 2010;45(5):457–76.CrossRefGoogle Scholar
  2. 2.
    Waris A, Nagpal G, Akhtar N. Use of nanotechnology in ophthalmology. Am J Drug Deliv Ther. 2014;1(2):073–6.Google Scholar
  3. 3.
    Sahoo SK, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discov Today. 2008;13(3):144–51.CrossRefGoogle Scholar
  4. 4.
    Minakaran N, Vafidis G, Mensah E. Proliferative diabetic retinopathy, maculopathy and choroidal neovascularization: concurrent pathology. Invest Ophthalmol Vis Sci. 2013;54(15):2433.Google Scholar
  5. 5.
    Xu Q, Kambhampati SP, Kannan RM. Nanotechnology approaches for ocular drug delivery. Middle East Afr J Ophthalmol. 2013;20(1):26–37.CrossRefPubMedCentralGoogle Scholar
  6. 6.
    Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev. 2006;58(11):1131–5.CrossRefGoogle Scholar
  7. 7.
    Shah SS, Denham LV, Elison JR, Bhattacharjee PS, Clement C, Huq T, Hill JM. Drug delivery to the posterior segment of the eye for pharmacologic therapy. Expert Rev Ophthalmol. 2010;5(1):75–93.CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Cunha-Vaz J. The blood-ocular barriers. Surv Ophthalmol. 1979;23(5):279–96.CrossRefGoogle Scholar
  9. 9.
    Campbell M, Humphries P. The blood-retina barrier: tight junctions and barrier modulation. Adv Exp Med Biol. 2012;763:70–84.PubMedGoogle Scholar
  10. 10.
    Hosoya K, Tachikawa M. The inner blood-retinal barrier: molecular structure and transport biology. Adv Exp Med Biol. 2012;763:85–104.PubMedGoogle Scholar
  11. 11.
    Rizzolo LJ, Peng S, Luo Y, Xiao W. Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium. Prog Retin Eye Res. 2011;30(5):296–323.CrossRefGoogle Scholar
  12. 12.
    Saha P, Kim K-J, Lee VH. A primary culture model of rabbit conjunctival epithelial cells exhibiting tight barrier properties. Curr Eye Res. 1996;15(12):1163–9.CrossRefGoogle Scholar
  13. 13.
    Reimondez-Troitiño S, Csaba N, Alonso M, De La Fuente M. Nanotherapies for the treatment of ocular diseases. Eur J Pharm Biopharm. 2015;95:279–93.CrossRefGoogle Scholar
  14. 14.
    Yañez-Soto B, Mannis MJ, Schwab IR, Li JY, Leonard BC, Abbott NL, Murphy CJ. Interfacial phenomena and the ocular surface. Ocul Surf. 2014;12(3):178–201.CrossRefGoogle Scholar
  15. 15.
    Webster TJ. Nanomedicine: what's in a definition? Int J Nanomedicine. 2006;1(2):115–6.CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Farjo KM, Ma J-x. The potential of nanomedicine therapies to treat neovascular disease in the retina. J Angiogenesi Res. 2010;2(1):21.CrossRefGoogle Scholar
  17. 17.
    Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145–60.CrossRefGoogle Scholar
  18. 18.
    Mishra GP, Bagui M, Tamboli V, Mitra AK. Recent applications of liposomes in ophthalmic drug delivery. J Drug Deliv. 2011;2011:14.CrossRefGoogle Scholar
  19. 19.
    Diederich F, Felber B. Supramolecular chemistry of dendrimers with functional cores. Proc Natl Acad Sci. 2002;99(8):4778–81.CrossRefGoogle Scholar
  20. 20.
    Dufès C, Uchegbu IF, Schätzlein AG. Dendrimers in gene delivery. Adv Drug Deliv Rev. 2005;57(15):2177–202.CrossRefGoogle Scholar
  21. 21.
    Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3(3):1377–97.CrossRefPubMedCentralGoogle Scholar
  22. 22.
    Panyam J, Dali MM, Sahoo SK, Ma W, Chakravarthi SS, Amidon GL, Levy RJ, Labhasetwar V. Polymer degradation and in vitro release of a model protein from poly (D, L-lactide-co-glycolide) nano-and microparticles. J Control Release. 2003;92(1):173–87.CrossRefGoogle Scholar
  23. 23.
    Duncan R. Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer. 2006;6(9):688–701.CrossRefGoogle Scholar
  24. 24.
    Panyam J, Zhou W-Z, Prabha S, Sahoo SK, Labhasetwar V. Rapid endo-lysosomal escape of poly (DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J. 2002;16(10):1217–26.CrossRefGoogle Scholar
  25. 25.
    Liu Z, Jiao Y, Wang Y, Zhou C, Zhang Z. Polysaccharides-based nanoparticles as drug delivery systems. Adv Drug Deliv Rev. 2008;60(15):1650–62.CrossRefGoogle Scholar
  26. 26.
    Zhang S, Uludağ H. Nanoparticulate systems for growth factor delivery. Pharm Res. 2009;26(7):1561–80.CrossRefGoogle Scholar
  27. 27.
    Nitta SK, Numata K. Biopolymer-based nanoparticles for drug/gene delivery and tissue engineering. Int J Mol Sci. 2013;14(1):1629–54.CrossRefPubMedCentralGoogle Scholar
  28. 28.
    Brivio D, Zygmanski P, Arnoldussen M, Hanlon J, Chell E, Sajo E, Makrigiorgos G, Ngwa W. Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation. Phys Med Biol. 2015;60(24):9203–13.CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Weng Y, Liu J, Jin S, Guo W, Liang X, Hu Z. Nanotechnology-based strategies for treatment of ocular disease. Acta Pharm Sin B. 2016;7:281–91.CrossRefPubMedCentralGoogle Scholar
  30. 30.
    Chaurasia SS, Lim RR, Lakshminarayanan R, Mohan RR. Nanomedicine approaches for corneal diseases. J Funct Biomater. 2015;6(2):277–98.CrossRefPubMedCentralGoogle Scholar
  31. 31.
    Shilo M, Sharon A, Baranes K, Motiei M, Lellouche J-PM, Popovtzer R. The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in vitro endothelial cell model. J Nanobiotechnol. 2015;13(1):19.CrossRefGoogle Scholar
  32. 32.
    Kemp MM, Kumar A, Mousa S, Dyskin E, Yalcin M, Ajayan P, Linhardt RJ, Mousa SA. Gold and silver nanoparticles conjugated with heparin derivative possess anti-angiogenesis properties. Nanotechnology. 2009;20(45):455104.CrossRefGoogle Scholar
  33. 33.
    Xu Y, Wen Z, Xu Z. Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma xenografts through an antiangiogenic mechanism. Anticancer Res. 2009;29(12):5103–9.PubMedGoogle Scholar
  34. 34.
    Al-Jamal KT, Akerman S, Podesta JE, Yilmazer A, Turton JA, Bianco A, Vargesson N, Kanthou C, Florence AT, Tozer GM. Systemic antiangiogenic activity of cationic poly-L-lysine dendrimer delays tumor growth. Proc Natl Acad Sci. 2010;107(9):3966–71.CrossRefGoogle Scholar
  35. 35.
    Sakurai E, Ozeki H, Kunou N, Ogura Y. Effect of particle size of polymeric nanospheres on intravitreal kinetics. Ophthalmic Res. 2000;33(1):31–6.CrossRefGoogle Scholar
  36. 36.
    Kim JH, Kim JH, Kim K-W, Kim MH, Yu YS. Intravenously administered gold nanoparticles pass through the blood–retinal barrier depending on the particle size, and induce no retinal toxicity. Nanotechnology. 2009;20(50):505101.CrossRefGoogle Scholar
  37. 37.
    Amrite AC, Kompella UB. Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration. J Pharm Pharmacol. 2005;57(12):1555–63.CrossRefGoogle Scholar
  38. 38.
    Amrite AC, Edelhauser HF, Singh SR, Kompella UB. Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration. Mol Vis. 2008;14:150–60.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Kim H, Robinson SB, Csaky KG. Investigating the movement of intravitreal human serum albumin nanoparticles in the vitreous and retina. Pharm Res. 2009;26(2):329–37.CrossRefGoogle Scholar
  40. 40.
    Sanders NN, Peeters L, Lentacker I, Demeester J, De Smedt SC. Wanted and unwanted properties of surface PEGylated nucleic acid nanoparticles in ocular gene transfer. J Control Release. 2007;122(3):226–35.CrossRefGoogle Scholar
  41. 41.
    Koo H, Moon H, Han H, Na JH, Huh MS, Park JH, Woo SJ, Park KH, Kwon IC, Kim K. The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection. Biomaterials. 2012;33(12):3485–93.CrossRefGoogle Scholar
  42. 42.
    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):771–81.CrossRefPubMedCentralGoogle Scholar
  43. 43.
    Misra GP, Singh RS, Aleman TS, Jacobson SG, Gardner TW, Lowe TL. Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina. Biomaterials. 2009;30(33):6541–7.CrossRefPubMedCentralGoogle Scholar
  44. 44.
    Sarao V, Veritti D, Boscia F, Lanzetta P. Intravitreal steroids for the treatment of retinal diseases. Sci World J. 2014;2014:14.CrossRefGoogle Scholar
  45. 45.
    Bourges J-L, Gautier SE, Delie F, Bejjani RA, Jeanny J-C, Gurny R, BenEzra D, Behar-Cohen FF. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Investig Ophthalmol Vis Sci. 2003;44(8):3562–9.CrossRefGoogle Scholar
  46. 46.
    Shelke NB, Kadam R, Tyagi P, Rao VR, Kompella UB. Intravitreal poly (L-lactide) microparticles sustain retinal and choroidal delivery of TG-0054, a hydrophilic drug intended for neovascular diseases. Drug Deliv Transl Res. 2011;1(1):76–90.CrossRefPubMedCentralGoogle Scholar
  47. 47.
    Gupta S, Velpandian T, Dhingra N, Jaiswal J. Intravitreal pharmacokinetics of plain and liposome-entrapped fluconazole in rabbit eyes. J Ocul Pharmacol Ther. 2000;16(6):511–8.CrossRefGoogle Scholar
  48. 48.
    Robinson R, Viviano SR, Criscione JM, Williams CA, Jun L, Tsai JC, Lavik EB. Nanospheres delivering the EGFR TKI AG1478 promote optic nerve regeneration: the role of size for intraocular drug delivery. Am Chem Soc NANO. 2011;5(6):4392–400.Google Scholar
  49. 49.
    Iezzi R, Guru BR, Glybina IV, Mishra MK, Kennedy A, Kannan RM. Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration. Biomaterials. 2012;33(3):979–88.CrossRefGoogle Scholar
  50. 50.
    Conley SM, Naash MI. Nanoparticles for retinal gene therapy. Prog Retin Eye Res. 2010;29(5):376–97.CrossRefPubMedCentralGoogle Scholar
  51. 51.
    Koirala A, Makkia RS, Cooper MJ, Naash MI. Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells. Biomaterials. 2011;32(35):9483–93.CrossRefPubMedCentralGoogle Scholar
  52. 52.
    Campbell M, Ozaki E, Humphries P. Systemic delivery of therapeutics to neuronal tissues: a barrier modulation approach. Expert Opin Drug Deliv. 2010;7(7):859–69.CrossRefGoogle Scholar
  53. 53.
    Campbell M, Nguyen AT, Kiang A-S, Tam LC, Gobbo OL, Kerskens C, Dhubhghaill SN, Humphries MM, Farrar G-J, Kenna PF. An experimental platform for systemic drug delivery to the retina. Proc Natl Acad Sci. 2009;106(42):17817–22.CrossRefGoogle Scholar
  54. 54.
    Singh S, Grossniklaus H, Kang S, Edelhauser H, Ambati BK, Kompella U. Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV. Gene Ther. 2009;16(5):645–59.CrossRefPubMedCentralGoogle Scholar
  55. 55.
    Abd A, Kanwar R, Kanwar J. Aged macular degeneration: current therapeutics for management and promising new drug candidates. Drug Discov Today. 2017;22:1671. Scholar
  56. 56.
    Milla P, Dosio F, Cattel L. PEGylation of proteins and liposomes: a powerful and flexible strategy to improve the drug delivery. Curr Drug Metab. 2012;13(1):105–19.CrossRefGoogle Scholar
  57. 57.
    Sharaf MG, Cetinel S, Heckler L, Damji K, Unsworth L, Montemagno C. Nanotechnology-based approaches for ophthalmology applications: therapeutic and diagnostic strategies. Asia Pac J Ophthalmol. 2014;3(3):172–80.CrossRefGoogle Scholar
  58. 58.
    Ferris FL, Wilkinson C, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR, Committee, BIfMRC. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120(4):844–51.CrossRefGoogle Scholar
  59. 59.
    Kanwar JR, Shankaranarayanan JS, Gurudevan S, Kanwar RK. Aptamer-based therapeutics of the past, present and future: from the perspective of eye-related diseases. Drug Discov Today. 2014;19(9):1309–21.CrossRefGoogle Scholar
  60. 60.
    Cheung AY, Rao P, Yonekawa Y, Thomas BJ, Shah A, Garretson BR, Capone A Jr, Hassan TS. Progressive massive choroidal neovascularization: a severe phenotype of refractory neovascular age-related macular degeneration. J Vitreoretin Dis. 2017;1(3):197–203.CrossRefGoogle Scholar
  61. 61.
    Kim H, Csaky KG. Nanoparticle–integrin antagonist C16Y peptide treatment of choroidal neovascularization in rats. J Control Release. 2010;142(2):286–93.CrossRefGoogle Scholar
  62. 62.
    Sriramoju B, Kanwar R, Veedu RN, Kanwar JR. Aptamer-targeted oligonucleotide theranostics: a smarter approach for brain delivery and the treatment of neurological diseases. Curr Top Med Chem. 2015;15(12):1115–24.CrossRefGoogle Scholar
  63. 63.
    Zehetner C, Kirchmair R, Huber S, Kralinger MT, Kieselbach GF. Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema. Br J Ophthalmol. 2013;97(4):454–9.CrossRefGoogle Scholar
  64. 64.
    Jin J, Zhou KK, Park K, Hu Y, Xu X, Zheng Z, Tyagi P, Kompella UB, Ma J-x. Anti-inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor. Investig Ophthalmol Vis Sci. 2011;52(9):6230–7.CrossRefGoogle Scholar
  65. 65.
    Marano R, Toth I, Wimmer N, Brankov M, Rakoczy P. 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):1544–50.CrossRefGoogle Scholar
  66. 66.
    Zhang C, Wang Y, Wu H, Zhang Z, Cai Y, Hou H, Zhao W, Yang X, Ma J. Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model. Gene Ther. 2010;17(3):338–51.CrossRefGoogle Scholar
  67. 67.
    Liu H-a, Liu Y-l, Ma Z-z, Wang J-c, Zhang Q. A lipid nanoparticle system improves siRNA efficacy in RPE cells and a laser-induced murine CNV model. Investig Ophthalmol Vis Sci. 2011;52(7):4789–94.CrossRefGoogle Scholar
  68. 68.
    Iriyama A, Oba M, Ishii T, Nishiyama N, Kataoka K, Tamaki Y, Yanagi Y. Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo. PLoS One. 2011;6(12):e28560.CrossRefPubMedCentralGoogle Scholar
  69. 69.
    Salehi-Had H, Roh MI, Giani A, Hisatomi T, Nakao S, Kim IK, Gragoudas ES, Vavvas D, Guccione S, Miller JW. Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. PLoS One. 2011;6(4):e18864.CrossRefPubMedCentralGoogle Scholar
  70. 70.
    Li F, Hurley B, Liu Y, Leonard B, Griffith M. Controlled release of bevacizumab through nanospheres for extended treatment of age-related macular degeneration. Open Ophthalmol J. 2012;6(1):54–8.CrossRefPubMedCentralGoogle Scholar
  71. 71.
    Hoshikawa A, Tagami T, Morimura C, Fukushige K, Ozeki T. Ranibizumab biosimilar/polyethyleneglycol-conjugated gold nanoparticles as a novel drug delivery platform for age-related macular degeneration. J Drug Deliv Sci Technol. 2017;38:45–50.CrossRefGoogle Scholar
  72. 72.
    Kanwar JR, Mohan RR, Kanwar RK, Roy K, Bawa R. Applications of aptamers in nanodelivery systems in cancer, eye and inflammatory diseases. Nanomedicine. 2010;5(9):1435–45.CrossRefGoogle Scholar
  73. 73.
    Vinores SA. Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263–8.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Herrero-Vanrell R, Cardillo JA, Kuppermann BD. Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema. Clin Ophthalmol. 2011;5:139–46.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Mansoor S, Kuppermann BD, Kenney MC. Intraocular sustained-release delivery systems for triamcinolone acetonide. Pharm Res. 2009;26(4):770–84.CrossRefGoogle Scholar
  76. 76.
    Iwase T, Fu J, Yoshida T, Muramatsu D, Miki A, Hashida N, Lu L, Oveson B, e Silva RL, Seidel C. Sustained delivery of a HIF-1 antagonist for ocular neovascularization. J Control Release. 2013;172(3):625–33.CrossRefGoogle Scholar
  77. 77.
    Sanford M. Fluocinolone acetonide intravitreal implant (Iluvien®). Drugs. 2013;73(2):187–93.PubMedGoogle Scholar
  78. 78.
    Ma L, Liu Y-L, Ma Z-Z, Dou H-L, Xu J-H, Wang J-C, Zhang X, Zhang Q. Targeted treatment of choroidal neovascularization using integrin-mediated sterically stabilized liposomes loaded with combretastatin A4. J Ocul Pharmacol Ther. 2009;25(3):195–200.CrossRefGoogle Scholar
  79. 79.
    Gross N, Ranjbar M, Evers C, Hua J, Martin G, Schulze B, Michaelis U, Hansen LL, Agostini HT. Choroidal neovascularization reduced by targeted drug delivery with cationic liposome-encapsulated paclitaxel or targeted photodynamic therapy with verteporfin encapsulated in cationic liposomes. Mol Vis. 2013;19:54–61.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Park K, Chen Y, Hu Y, Mayo AS, Kompella UB, Longeras R, Ma J-x. Nanoparticle-mediated expression of an angiogenic inhibitor ameliorates ischemia-induced retinal neovascularization and diabetes-induced retinal vascular leakage. Diabetes. 2009;58(8):1902–13.CrossRefPubMedCentralGoogle Scholar
  81. 81.
    Benny O, Nakai K, Yoshimura T, Bazinet L, Akula JD, Nakao S, Hafezi-Moghadam A, Panigrahy D, Pakneshan P, D'Amato RJ. Broad spectrum antiangiogenic treatment for ocular neovascular diseases. PLoS One. 2010;5(9):e12515.CrossRefPubMedCentralGoogle Scholar
  82. 82.
    Falavarjani KG, Nguyen QD. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye. 2013;27(7):787–94.CrossRefGoogle Scholar
  83. 83.
    Rechtman E, Harris A, Garzozi HJ, Ciulla TA. Pharmacologic therapies for diabetic retinopathy and diabetic macular edema. Clin Ophthalmol. 2007;1(4):383–91.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Araújo J, Nikolic S, Egea MA, Souto EB, Garcia ML. Nanostructured lipid carriers for triamcinolone acetonide delivery to the posterior segment of the eye. Colloids Surf B: Biointerfaces. 2011;88(1):150–7.CrossRefGoogle Scholar
  85. 85.
    Fangueiro JF, Silva AM, Garcia ML, Souto EB. Current nanotechnology approaches for the treatment and management of diabetic retinopathy. Eur J Pharm Biopharm. 2015;95:307–22.CrossRefGoogle Scholar
  86. 86.
    Araújo J, Garcia ML, Mallandrich M, Souto EB, Calpena AC. Release profile and transscleral permeation of triamcinolone acetonide loaded nanostructured lipid carriers (TA-NLC): in vitro and ex vivo studies. Nanomedicine. 2012;8(6):1034–41.CrossRefGoogle Scholar
  87. 87.
    B.a. Lomb, Retisert [package insert], Rochester, NY, 2009.
  88. 88.
    Thériault BL, Dimaras H, Gallie BL, Corson TW. The genomic landscape of retinoblastoma: a review. Clin Exp Ophthalmol. 2014;42(1):33–52.CrossRefGoogle Scholar
  89. 89.
    Kang SJ, Durairaj C, Kompella UB, O’Brien JM, Grossniklaus HE. Subconjunctival nanoparticle carboplatin in the treatment of murine retinoblastoma. Arch Ophthalmol. 2009;127(8):1043–7.CrossRefPubMedCentralGoogle Scholar
  90. 90.
    Boddu SH, Jwala J, Chowdhury MR, Mitra AK. In vitro evaluation of a targeted and sustained release system for retinoblastoma cells using doxorubicin as a model drug. J Ocul Pharmacol Ther. 2010;26(5):459–68.CrossRefPubMedCentralGoogle Scholar
  91. 91.
    Gary-Bobo M, Mir Y, Rouxel C, Brevet D, Hocine O, Maynadier M, Gallud A, Da Silva A, Mongin O, Blanchard-Desce M. Multifunctionalized mesoporous silica nanoparticles for the in vitro treatment of retinoblastoma: drug delivery, one and two-photon photodynamic therapy. Int J Pharm. 2012;432(1):99–104.CrossRefGoogle Scholar
  92. 92.
    Venkatesan N, Kanwar JR, Deepa PR, Navaneethakrishnan S, Joseph C, Krishnakumar S. Targeting HSP90/Survivin using a cell permeable structure based peptido-mimetic shepherdin in retinoblastoma. Chem Biol Interact. 2016;252:141–9.CrossRefGoogle Scholar
  93. 93.
    Samuel J, Singh N, Kanwar JR, Krishnakumar S, Kanwar RK. Upregulation of sodium iodide symporter (NIS) protein expression by an innate immunity component: promising potential for targeting radiosensitive retinoblastoma. Exp Eye Res. 2015;139:108–14.CrossRefGoogle Scholar
  94. 94.
    Ahmed F, Ali MJ, Kondapi AK. Carboplatin loaded protein nanoparticles exhibit improve anti-proliferative activity in retinoblastoma cells. Int J Biol Macromol. 2014;70:572–82.CrossRefGoogle Scholar
  95. 95.
    Kuchtey J, Kuchtey RW. The microfibril hypothesis of glaucoma: implications for treatment of elevated intraocular pressure. J Ocul Pharmacol Ther. 2014;30(2–3):170–80.CrossRefPubMedCentralGoogle Scholar
  96. 96.
    Chang EE, Goldberg JL. Glaucoma 2.0: neuroprotection, neuroregeneration, neuroenhancement. Ophthalmology. 2012;119(5):979–86.CrossRefPubMedCentralGoogle Scholar
  97. 97.
    Wadhwa S, Paliwal R, Paliwal SR, Vyas S. Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation. J Drug Target. 2010;18(4):292–302.CrossRefGoogle Scholar
  98. 98.
    Zhao L, Chen G, Li J, Fu Y, Mavlyutov TA, Yao A, Nickells RW, Gong S, Guo LW. An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration. J Control Release. 2017;10(247):153–66.CrossRefGoogle Scholar
  99. 99.
    Bhagav P, Upadhyay H, Chandran S. Brimonidine tartrate–eudragit long-acting nanoparticles: formulation, optimization, in vitro and in vivo evaluation. AAPS PharmSciTech. 2011;12(4):1087–101.CrossRefPubMedCentralGoogle Scholar
  100. 100.
    Jung HJ, Abou-Jaoude M, Carbia BE, Plummer C, Chauhan A. Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses. J Control Release. 2013;165(1):82–9.CrossRefGoogle Scholar
  101. 101.
    Schwartz KS, Lee RK, Gedde SJ. Glaucoma drainage implants: a critical comparison of types. Curr Opin Ophthalmol. 2006;17(2):181–9.CrossRefGoogle Scholar
  102. 102.
    Checa-Casalengua P, Jiang C, Bravo-Osuna I, Tucker BA, Molina-Martínez IT, Young MJ, Herrero-Vanrell R. Retinal ganglion cells survival in a glaucoma model by GDNF/Vit E PLGA microspheres prepared according to a novel microencapsulation procedure. J Control Release. 2011;156(1):92–100.CrossRefGoogle Scholar
  103. 103.
    Jeun M, Jeoung JW, Moon S, Kim YJ, Lee S, Paek SH, Chung K-W, Park KH, Bae S. Engineered superparamagnetic Mn 0.5 Zn 0.5 Fe 2 O 4 nanoparticles as a heat shock protein induction agent for ocular neuroprotection in glaucoma. Biomaterials. 2011;32(2):387–94.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Afrah Jalil Abd
    • 1
  • Rupinder Kaur Kanwar
    • 1
  • Yashwant V. Pathak
    • 2
  • Maysaa Al Mohammedawi
    • 1
  • Jagat Rakesh Kanwar
    • 1
    Email author
  1. 1.Nanomedicine Laboratory of Immunology and Molecular Biochemical Research (NLIMBR), Centre Molecular and Medical Research (CMMR), School of Medicine, Faculty of Health, Geelong, Deakin UniversityWarn Ponds, GeelongAustralia
  2. 2.College of Pharmacy, University of South Florida HealthTampaUSA

Personalised recommendations