404
Views
16
CrossRef citations to date
0
Altmetric
Review

Recent advances in intraocular and novel drug delivery systems for the treatment of diabetic retinopathy

, , , , , , , , , & show all
Pages 553-576 | Received 04 Apr 2020, Accepted 02 Nov 2020, Published online: 14 Dec 2020

References

  • Zaccardi F, Webb DR, Yates T, et al. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J. 2016 Feb;92(1084):63–69.
  • Kim JH, Kim JH, Kim KW, et al. Intravenously administered gold nanoparticles pass through the blood-retinal barrier depending on the particle size, and induce no retinal toxicity. Nanotechnology. 2009 Dec 16;20(50):505101.
  • Cao Y, Samy KE, Bernards DA, et al., Recent advances in intraocular sustained-release drug delivery devices. Drug Discov Today. 24(8): 1694–1700. 2019.
  • Reardon G, Kotak S, Schwartz GF. Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: a systematic review. Patient Prefer Adherence. 2011;5:441–463.
  • Rofagha S, Bhisitkul RB, Boyer DS, et al. Seven-year outcomes in ranibizumab-treated patients in anchor, marina, and horizon: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120(11):2292–2299.
  • Haller JA, Bandello F, Belfort R Jr, et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134–1146. e3.
  • Callanan DG, Jaffe GJ, Martin DF, et al. Treatment of posterior uveitis with a fluocinolone acetonide implant. Arch Ophthalmol. 2008;126(9):1191–1201.
  • Fangueiro JF, Silva AM, Garcia ML, et al. Current nanotechnology approaches for the treatment and management of diabetic retinopathy. Eur J Pharm Biopharm. 2015;95:307–322.
  • Fangueiro J, Gonzalez-Mira E, Martins-Lopes P, et al. A novel lipid nanocarrier for insulin delivery: production, characterization and toxicity testing. Pharm Dev Technol. 2013;18(3):545–549.
  • Fangueiro JF, Silva AM, Garcia ML, et al. Current nanotechnology approaches for the treatment and management of diabetic retinopathy. Eur J Pharm Biopharm. 2015 Sep;95(Pt B):307–322.
  • Amadio M, Bucolo C, Leggio G, et al. The PKCβ/HuR/VEGF pathway in diabetic retinopathy. Biochem Pharmacol. 2010;80(8):1230–1237.
  • Lechner J, O’Leary OE, Stitt AW. The pathology associated with diabetic retinopathy. Vision Res. 2017;139:7–14.
  • Platania CBM, Leggio GM, Drago F, et al. Computational systems biology approach to identify novel pharmacological targets for diabetic retinopathy. Biochem Pharmacol. 2018;158:13–26.
  • Barot M, Gokulgandhi MR, Mitra AK. Mitochondrial dysfunction in retinal diseases. Curr Eye Res. 2011 Dec;36(12):1069–1077.
  • Miwa K, Nakamura J, Hamada Y, et al. The role of polyol pathway in glucose-induced apoptosis of cultured retinal pericytes. Diabetes Res Clin Pract. 2003 Apr;60(1):1–9.
  • Naruse K, Nakamura J, Hamada Y, et al. Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes. Exp Eye Res. 2000 Sep;71(3):309–315.
  • Platania CBM, Lazzara F, Fidilio A, et al. Blood-retinal barrier protection against high glucose damage: the role of P2X7 receptor. Biochem Pharmacol. 2019 Oct;168:249–258.
  • Platania CBM, Giurdanella G, Di Paola L, et al. P2X7 receptor antagonism: implications in diabetic retinopathy. Biochem Pharmacol. 2017 Aug 15;138:130–139.
  • Tsai T, Kuehn S, Tsiampalis N, et al. Anti-inflammatory cytokine and angiogenic factors levels in vitreous samples of diabetic retinopathy patients. PLoS One. 2018;13(3):1–13.
  • Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes. 1998 Jun;47(6):859–866.
  • Amadio M, Pascale A, Cupri S, et al. Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat. Pharmacol Res. 2016 Sep;111:713–720.
  • Gardiner TA, Anderson HR, Stitt AW. Inhibition of advanced glycation end-products protects against retinal capillary basement membrane expansion during long-term diabetes. J Pathol. 2003 Oct;201(2):328–333.
  • Friedman EA. Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications. Diabetes Care. 1999 Mar;22(Suppl 2):B65–71.
  • Nakamura M, Barber AJ, Antonetti DA, et al. Excessive hexosamines block the neuroprotective effect of insulin and induce apoptosis in retinal neurons. J Biol Chem. 2001 Nov 23;276(47):43748–43755.
  • Franken AA, Derkx FH, Schalekamp MA, et al. Association of high plasma prorenin with diabetic retinopathy. J Hypertens Suppl. 1988 Dec;6(4):S461–463.
  • Luetscher JA, Kraemer FB, Wilson DM, et al. Increased plasma inactive renin in diabetes mellitus. N Engl J Med. 1985;312(22):1412–1417.
  • Elakkiya M, Selvaraj K, Current KG. Emerging therapies for the management of diabetic retinopathy. J Appl Pharm Sci. 2017;7(9):243–251.
  • Barber AJ. A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Apr;27(2):283–290.
  • Seki M, Tanaka T, Nawa H, et al. Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells. Diabetes. 2004 Sep;53(9):2412–2419.
  • Liu Y, Tao L, Fu X, et al. BDNF protects retinal neurons from hyperglycemia through the TrkB/ERK/MAPK pathway. Mol Med Rep. 2013 Jun;7(6):1773–1778.
  • Ola MS, Nawaz MI, El-Asrar AA, et al. Reduced levels of brain derived neurotrophic factor (BDNF) in the serum of diabetic retinopathy patients and in the retina of diabetic rats. Cell Mol Neurobiol. 2013 Apr;33(3):359–367.
  • Chitranshi N, Gupta V, Kumar S, et al. Exploring the molecular interactions of 7,8-Dihydroxyflavone and its derivatives with TrkB and VEGFR2 proteins. Int J Mol Sci. 2015 Sep;16(9):21087–21108.
  • Chitranshi N, Dheer Y, Gupta V, et al. PTPN11 induces endoplasmic stress and apoptosis in SH-SY5Y cells. Neuroscience. 2017 Nov 19;364:175–189.
  • Chitranshi N, Dheer Y, Mirzaei M, et al. Loss of Shp2 rescues BDNF/TrkB signaling and contributes to improved retinal ganglion cell neuroprotection. Mol Ther. 2019 Feb 6;27(2):424–441.
  • Lu L, Jiang Y, Jaganathan R, et al. Current advances in pharmacotherapy and technology for diabetic retinopathy: A systematic review. J Ophthalmol. 2018;2018:1694187..
  • Danis RP, Ciulla TA, Pratt LM, et al. Intravitreal triamcinolone acetonide in exudative age-related macular degeneration. Retina. 2000;20(3):244–250.
  • Sheshala R, Hong GC, Yee WP, et al. In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide. Drug Deliv Transl Res. 2019;9(2):534–542.
  • McAvoy K, Jones D, Thakur RRS. Synthesis and characterisation of photocrosslinked poly (ethylene glycol) diacrylate implants for sustained ocular drug delivery. Pharm Res. 2018;35(2):1–17.
  • Haller JA. Intraocular steroids in the office. New formulations offer preservative-free triamcinolone without relying on compounding pharmacies. Retin Phys. 2009;1:45–47.
  • PIERAMICI DJ. I-vation implant technology. Retin Physician. 2007;4(7):24–25.
  • Campochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):626–635 e2.
  • Jaffe GJ, Martin D, Callanan D, et al. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four–week results of a multicenter randomized clinical study. Ophthalmology. 2006;113(6):1020–1027.
  • Pacella F, Ferraresi AF, Turchetti P, et al. Intravitreal injection of Ozurdex® implant in patients with persistent diabetic macular edema, with six-month follow-up. Ophthalmol Eye Dis. 2016;8:11–16.
  • Lee SS, Yuan SSP, Robinson SSPMR Ocular implants for drug delivery. Encyclopedia of biomaterials and biomedical engineering: CRC Press; 2008. p. 1981–1995.
  • Bode C, Kranz H, Siepmann F, et al. In-situ forming PLGA implants for intraocular dexamethasone delivery. Int J Pharm. 2018;548(1):337–348.
  • Bucolo C, Gozzo L, Longo L, et al., Long-term efficacy and safety profile of multiple injections of intravitreal dexamethasone implant to manage diabetic macular edema: a systematic review of real-world studies. J Pharmacol Sci. 138(4): 219–232. 2018.
  • Gupta M, Majumdar D. Effect of concentration, pH, and preservative on in vitro transcorneal permeation of ibuprofen and flurbiprofen from non-buffered aqueous drops. Indian J Exp Bio. 1997;35(8):844–849.
  • Ahuja M, Dhake AS, Majumdar DK. Effect of formulation factors on in vitro permeation of diclofenac from experimental and marketed aqueous eye drops through excised goat cornea. Yakugaku Zasshi. 2006;126(12):1369–1375.
  • Miyamoto K, Khosrof S, Bursell SE, et al. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10836–10841.
  • Kern TS, Miller CM, Du Y, et al. Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology. Diabetes. 2007 Feb;56(2):373–379.
  • Zheng L, Howell SJ, Hatala DA, et al. Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy. Diabetes. 2007 Feb;56(2):337–345.
  • Valiatti FB, Crispim D, Benfica C, et al. [The role of vascular endothelial growth factor in angiogenesis and diabetic retinopathy]. Arq Bras Endocrinol Metabol. 2011 Mar;55(2):106–113.
  • Gragoudas ES, Adamis AP, Cunningham ET Jr, et al. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004;351(27):2805–2816.
  • Schmidinger G, Maar N, Bolz M, et al. Repeated intravitreal bevacizumab (Avastin((R))) treatment of persistent new vessels in proliferative diabetic retinopathy after complete panretinal photocoagulation. Acta Ophthalmol. 2011 Feb;89(1):76–81.
  • Vaishya R, Khurana V, Patel S, et al. Long-term delivery of protein therapeutics. Expert Opin Drug Deliv. 2015;12(3):415–440.
  • Badiee P, Varshochian R, Rafiee‐Tehrani M, et al. Ocular implant containing bevacizumab‐loaded chitosan nanoparticles intended for choroidal neovascularization treatment. J Biomed Mater Res A. 2018;106(8):2261–2271.
  • Matsumiya W, Honda S, Bessho H, et al. Early responses to intravitreal ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. J Ophthalmol. 2011;2011:742020.
  • Moradi A, Sepah YJ, Sadiq MA, et al. Vascular endothelial growth factor trap-eye (Aflibercept) for the management of diabetic macular edema. World J Diabetes. 2013 Dec 15;4(6):303–309.
  • Khanna S, Komati R, Eichenbaum DA, et al. Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review. BMJ Open Ophthalmol. 2019;4(1):1–8.
  • Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127(1):72–84.
  • Khurana R. Safety and efficacy of abicipar in patients with neovascular age-related macular degeneration. Lect Present Am Acad Ophthalmol. 2018;9(3):250–259.
  • Kuppermann BD, Thomas EL, de Smet MD, et al. Safety results of two phase III trials of an intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage. Am J Ophthalmol. 2005 Oct;140(4):585–597.
  • Lopez-Lopez F, Rodriguez-Blanco M, Gomez-Ulla F, et al. Enzymatic vitreolysis. Curr Diabetes Rev. 2009 Feb;5(1):57–62.
  • Varma R, Haller JA, Kaiser PK. Improvement in patient-reported visual function after ocriplasmin for vitreomacular adhesion: results of the microplasmin for intravitreous injection-traction release without surgical treatment (MIVI-TRUST) trials. JAMA Ophthalmol. 2015 Sep;133(9):997–1004.
  • Chen XR, Besson VC, Palmier B, et al. Neurological recovery-promoting, anti-inflammatory, and anti-oxidative effects afforded by fenofibrate, a PPAR alpha agonist, in traumatic brain injury. J Neurotrauma. 2007 Jul;24(7):1119–1131.
  • Scott R, Best J, Forder P, et al. Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481]. Cardiovasc Diabetol. 2005;4:13.
  • Keech AC, Mitchell P, Summanen P, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370(9600):1687–1697.
  • Group AS, Group AES. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363(3):233–244.
  • Athyros VG, Kakafika AI, Tziomalos K, et al. Pleiotropic effects of statins-clinical evidence. Curr Pharm Des. 2009;15(5):479–489.
  • Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89–118.
  • Hata Y, Miura M, Asato R, et al. Antiangiogenic mechanisms of simvastatin in retinal endothelial cells. Graefe’s Arch Clin Exp Ophthalmol. 2010;248(5):667–673.
  • Dorecka M, Francuz T, Garczorz W, et al. The influence of elastin degradation products, glucose and atorvastatin on metalloproteinase-1,-2,-9 and tissue inhibitor of metalloproteinases-1,-2,-3 expression in human retinal pigment epithelial cells. Acta Biochim Pol. 2014;61(2):265–270.
  • Nagaoka T, Hein TW, Yoshida A, et al. Simvastatin elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and mevalonate-rho kinase pathways. Invest Ophthalmol Vis Sci. 2007;48(2):825–832.
  • Fernandes R, Bento CF, Matafome P, et al. Atorvastatin-mediated protection of the retina in a model of diabetes with hyperlipidemia. Can J Physiol Pharmacol. 2014;92(12):1037–1043.
  • Al-Shabrawey M, Bartoli M, El-Remessy AB, et al. Role of NADPH oxidase and Stat3 in statin-mediated protection against diabetic retinopathy. Invest Ophthalmol Vis Sci. 2008;49(7):3231–3238.
  • Li J, Wang JJ, Yu Q, et al. Inhibition of reactive oxygen species by Lovastatin downregulates vascular endothelial growth factor expression and ameliorates blood-retinal barrier breakdown in db/db mice: role of NADPH oxidase 4. Diabetes. 2010;59(6):1528–1538.
  • Li J, Wang JJ, Chen D, et al. Systemic administration of HMG-CoA reductase inhibitor protects the blood–retinal barrier and ameliorates retinal inflammation in type 2 diabetes. Exp Eye Res. 2009;89(1):71–78.
  • Miyahara S, Kiryu J, Yamashiro K, et al. Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes. Am J Pathol. 2004;164(5):1697–1706.
  • Dal Monte M, Ristori C, Cammalleri M, et al. Effects of somatostatin analogues on retinal angiogenesis in a mouse model of oxygen-induced retinopathy: involvement of the somatostatin receptor subtype 2. Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3596–3606.
  • Panagiotoglou TD, Ganotakis ES, Kymionis GD, et al. Atorvastatin for diabetic macular edema in patients with diabetes mellitus and elevated serum cholesterol. Ophthalmic Surg Lasers Imaging Retina. 2010;41(3):316–322.
  • Gupta A, Gupta V, Thapar S, et al. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am J Ophthalmol. 2004;137(4):675–682.
  • Vaajanen A, Lakkisto P, Virtanen I, et al. Angiotensin receptors in the eyes of arterial hypertensive rats. Acta Ophthalmol. 2010 Jun;88(4):431–438.
  • Mauer M, Zinman B, Gardiner R, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009 Jul 2;361(1):40–51.
  • Willis LM, El-Remessy AB, Somanath PR, et al. Angiotensin receptor blockers and angiogenesis: clinical and experimental evidence. Clin Sci (Lond). 2011 Apr;120(8):307–319.
  • Chaturvedi N, Porta M, Klein R, et al. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet. 2008 Oct 18;372(9647):1394–1402.
  • Baudoin C, Passa P, Sharp P, et al. Effect of aspirin alone and aspirin plus dipyridamole in early diabetic-retinopathy - a multicenter randomized controlled clinical-trial. Diabetes. 1989 Apr;38(4):491–498.
  • Satofuka S, Ichihara A, Nagai N, et al. (Pro)renin receptor-mediated signal transduction and tissue renin-angiotensin system contribute to diabetes-induced retinal inflammation. Diabetes. 2009 Jul;58(7):1625–1633.
  • Selvaraj K, Gowthamarajan K, Karri VV, et al. Current treatment strategies and nanocarrier based approaches for the treatment and management of diabetic retinopathy. J Drug Target. 2017 Jun;25(5):386–405.
  • Takahashi K, Saishin Y, Saishin Y, et al. Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib. Arch Ophthalmol. 2009 Apr;127(4):494–499.
  • Aiello LP, Vignati L, Sheetz MJ, et al. Oral protein kinase C beta inhibition using ruboxistaurin efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the protein kinase C beta inhibitor-diabetic retinopathy study and the protein kinase C beta inhibitor-diabetic retinopathy study 2. Retina-J Ret Vit Dis. 2011 Nov;31(10):2084–2094.
  • Poulsen JE. Recovery from retinopathy in a case of diabetes with Simmonds’ disease. Diabetes. 1953 Jan-Feb;2(1):7–12.
  • Dal Monte M, Ristori C, Cammalleri M, et al. Effects of somatostatin analogues on retinal angiogenesis in a mouse model of oxygen-induced retinopathy: involvement of the somatostatin receptor subtype 2. Invest Ophthalmol Vis Sci. 2009;50(8):3596–3606.
  • Grant MB, Mames RN, Fitzgerald C, et al. The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study. Diabetes Care. 2000;23(4):504–509.
  • Henry RP. Multiple roles of carbonic anhydrase in cellular transport and metabolism. Annu Rev Physiol. 1996;58(1):523–538.
  • Wang C-Z, Basila D, Aung HH, et al. Effects of Ganoderma lucidum extract on chemotherapy-induced nausea and vomiting in a rat model. Am J Chin Med. 2005;33(5):807–815.
  • Agrawal SS, Naqvi S, Gupta SK, et al. Prevention and management of diabetic retinopathy in STZ diabetic rats by Tinospora cordifolia and its molecular mechanisms. Food Chem Toxicol. 2012;50(9):3126–3132.
  • Halim EM, Mukhopadhyay A. Effect ofOcimum sanctum (Tulsi) and vitamin E on biochemical parameters and retinopathy in streptozotocin induced diabetic rats. Indian J Clin Biochem. 2006;21(2):181–188.
  • Aldebasi YH, Aly SM, Rahmani AH. Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathways. Int J Physiol Pathophysiol Pharmacol. 2013;5(4):194–202.
  • Gupta SK, Kumar B, Nag TC, et al. Curcumin prevents experimental diabetic retinopathy in rats through its hypoglycemic, antioxidant, and anti-inflammatory mechanisms. J Ocul Pharmacol Ther. 2011;27(2):123–130.
  • Bucolo C, Drago F, Maisto R, et al., Curcumin prevents high glucose damage in retinal pigment epithelial cells through ERK1/2‐mediated activation of the Nrf2/HO‐1 pathway. J Cell Physiol. 234(10): 17295–17304. 2019.
  • Alshamrani M, Sikder S, Coulibaly F, et al. Self-assembling topical nanomicellar formulation to improve curcumin absorption across ocular tissues. AAPS PharmSciTech. 2019;20(7):1–16.
  • Steigerwalt R, Belcaro G, Cesarone MR, et al. Pycnogenol® improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther. 2009;25(6):537–540.
  • Nakajima M, Cooney MJ, Tu AH, et al. Normalization of retinal vascular permeability in experimental diabetes with genistein. Invest Ophthalmol Vis Sci. 2001;42(9):2110–2114.
  • Kumar B, Gupta SK, Nag TC, et al. Green tea prevents hyperglycemia-induced retinal oxidative stress and inflammation in streptozotocin-induced diabetic rats. Ophthalmic Res. 2012;47(2):103–108.
  • Parveen A, Kim JH, Oh BG, et al. Phytochemicals: target-based therapeutic strategies for diabetic retinopathy. Molecules. 2018;23(7):1–30.
  • Neal SE, Buehne KL, Besley NA, et al. Resveratrol protects against hydroquinone-induced oxidative threat in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2020;61(4):1–12.
  • Gonzalez VH, Giuliari GP, Banda RM, et al. Intravitreal injection of pegaptanib sodium for proliferative diabetic retinopathy. Br J Ophthalmol. 2009 Nov;93(11):1474–1478.
  • Group DS. Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy: a multicenter randomized controlled clinical trial. Diabetes. 1989;38(4):491–498.
  • Grant MB, Caballero S Jr. The potential role of octreotide in the treatment of diabetic retinopathy. Treat Endocrinol. 2005;4(4):199–203.
  • Henry RP. Multiple roles of carbonic anhydrase in cellular transport and metabolism. Annu Rev Physiol. 1996;58:523–538.
  • Gonzalez-Cordero A, West EL, Pearson RA, et al. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nat Biotechnol. 2013;31(8):741–747.
  • Bucolo C, Drago F, Salomone S. Ocular drug delivery: a clue from nanotechnology. Front Pharmacol. 2012;3:1–3.
  • Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):1–9.
  • Kompella UB, Amrite AC, Ravi RP, et al. Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res. 2013 Sep;36:172–198.
  • Elsaid N, Somavarapu S, Jackson TL. Cholesterol-poly(ethylene) glycol nanocarriers for the transscleral delivery of sirolimus. Exp Eye Res. 2014 Apr;121:121–129.
  • Rajala A, Wang YH, Zhu Y, et al. Nanoparticle-assisted targeted delivery of eye-specific genes to eyes significantly improves the vision of blind mice in vivo. Nano Lett. 2014 Sep;14(9):5257–5263.
  • Bogdanov P, Sampedro J, Solà-Adell C, et al. Effects of liposomal formulation of citicoline in experimental diabetes-induced retinal neurodegeneration. Int J Mol Sci. 2018;19(8):1–15.
  • Tan G, Yu S, Pan H, et al. Bioadhesive chitosan-loaded liposomes: a more efficient and higher permeable ocular delivery platform for timolol maleate. Int J Biol Macromol. 2017;94:355–363.
  • Joseph RR, Tan DWN, Ramon MRM, et al. Characterization of liposomal carriers for the trans-scleral transport of Ranibizumab. Sci Rep. 2017;7(1):1–10.
  • Kawakami S, Harada A, Sakanaka K, et al. In vivo gene transfection via intravitreal injection of cationic liposome/plasmid DNA complexes in rabbits. Int J Pharm. 2004;278(2):255–262.
  • Bochot A, Fattal E, Boutet V, et al. Intravitreal delivery of oligonucleotides by sterically stabilized liposomes. Invest Ophthalmol Vis Sci. 2002;43(1):253–259.
  • Campos EJ, Campos A, Martins J, et al. Opening eyes to nanomedicine: where we are, challenges and expectations on nanotherapy for diabetic retinopathy. Nanomedicine. 2017;13(6):2101–2113.
  • Wang Y, Liu CH, Ji T, et al. Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles. Nat Commun. 2019 Feb 18;10(1):1–9.
  • Amato R, Dal Monte M, Lulli M, et al. Nanoparticle-mediated delivery of neuroprotective substances for the treatment of diabetic retinopathy. Curr Neuropharmacol. 2018;16(7):993–1003.
  • Nor NM, Guo CX, Rupenthal ID, et al. Sustained connexin43 mimetic peptide release from loaded nanoparticles reduces retinal and choroidal photodamage. Invest Opthalmol Visual Sci. 2018;59(8):3682–3693.
  • Amadio M, Pascale A, Cupri S, et al. Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat. Pharmacol Res. 2016;111:713–720.
  • Jaiswal M, Dudhe R, Sharma P. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015;5(2):123–127.
  • Patel N, Nakrani H, Raval M, et al. Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability. Drug Deliv. 2016;23(9):3712–3723.
  • Cholkar K, Patel A, Dutt Vadlapudi A, et al. Novel nanomicellar formulation approaches for anterior and posterior segment ocular drug delivery. Recent Pat Nanomed. 2012;2(2):82–95.
  • Chopra P, Hao J, Li SK. Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera. J Control Release. 2012;160(1):96–104.
  • Vaishya RD, Gokulgandhi M, Patel S, et al. Novel dexamethasone-loaded nanomicelles for the intermediate and posterior segment uveitis. Aaps Pharmscitech. 2014;15(5):1238–1251.
  • Mandal A, Gote V, Pal D, et al. Ocular pharmacokinetics of a topical ophthalmic nanomicellar solution of cyclosporine (Cequa®) for dry eye disease. Pharm Res. 2019;36(2):36.
  • Kaur IP, Kakkar S. Nanotherapy for posterior eye diseases. J Control Release. 2014 Nov 10;193:100–112.
  • Amato R, Dal Monte M, Lulli M, et al. Nanoparticle-mediated delivery of neuroprotective substances for the treatment of diabetic retinopathy. Curr Neuropharmacol. 2018;16(7):993–1003.
  • Tatke A, Dudhipala N, Janga KY, et al. In situ gel of triamcinolone acetonide-loaded solid lipid nanoparticles for improved topical ocular delivery: tear kinetics and ocular disposition studies. Nanomaterials (Basel). 2019 27;9(1):1–17.
  • Ahangarpour A, Oroojan AA, Khorsandi L, et al. Solid lipid nanoparticles of myricitrin have antioxidant and antidiabetic effects on streptozotocin-nicotinamide-induced diabetic model and myotube cell of male mouse. Oxid Med Cell Longev. 2018;2018:7496936.
  • Shazly GA. Ciprofloxacin controlled-solid lipid nanoparticles: characterization, in vitro release, and antibacterial activity assessment. Biomed Res Int. 2017;2017. DOI:10.1155/2017/2120734.
  • Del Pozo-Rodriguez A, Delgado D, Solinis M, et al. Solid lipid nanoparticles for retinal gene therapy: transfection and intracellular trafficking in RPE cells. Int J Pharm. 2008;360(1–2):177–183.
  • Iezzi R, Guru BR, Glybina IV, et al. Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration. Biomaterials. 2012;33(3):979–988.
  • Kambhampati SP, Clunies-Ross AJ, Bhutto I, et al. Systemic and intravitreal delivery of dendrimers to activated microglia/macrophage in ischemia/reperfusion mouse retina. Invest Ophthalmol Vis Sci. 2015;56(8):4413–4424.
  • Yavuz B, Pehlivan SB, Vural İ, et al. In vitro/in vivo evaluation of dexamethasone—PAMAM dendrimer complexes for retinal drug delivery. J Pharm Sci. 2015;104(11):3814–3823.
  • Wimmer N, Marano RJ, Kearns PS, et al. Syntheses of polycationic dendrimers on lipophilic peptide core for complexation and transport of oligonucleotides. Bioorg Med Chem Lett. 2002;12(18):2635–2637.
  • Bejjani RA, BenEzra D, Cohen H, et al. Nanoparticles for gene delivery to retinal pigment epithelial cells. Mol Vis. 2005;11(2):124–132.
  • Bourges J-L, Gautier SE, Delie F, et al. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Ophthalmol Vis Sci. 2003;44(8):3562–3569.
  • Selvaraj K, Kuppusamy G, Krishnamurthy J, et al., Repositioning of itraconazole for the management of ocular neovascularization through surface-modified nanostructured lipid carriers. Assay Drug Dev Technol. 17(4): 178–190. 2019.
  • Paterniti I, Di Paola R, Campolo M, et al. Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2015;769:313–323.
  • Platania CBM, Dei Cas M, Cianciolo S, et al. Novel ophthalmic formulation of myriocin: implications in retinitis pigmentosa. Drug Deliv. 2019;26(1):237–243.
  • Lowe T, Misra G, Daley D, et al. Tailored nanogels for controlled delivery of therepeutics across ocular biological barriers. Invest Ophthalmol Vis Sci. 2009;50(13):2425.
  • Zhang J, Misra GP, Chang SP, et al. Charged nanogels efficiently overcome ocular biological barriers. Invest Ophthalmol Vis Sci. 2011;52(14):429.
  • Nasr FH, Khoee S. Design, characterization and in vitro evaluation of novel shell crosslinked poly (butylene adipate)-co-N-succinyl chitosan nanogels containing loteprednol etabonate: a new system for therapeutic effect enhancement via controlled drug delivery. Eur J Med Chem. 2015;102:132–142.
  • Jamard M, Hoare T, Sheardown H. Nanogels of methylcellulose hydrophobized with N-tert-butylacrylamide for ocular drug delivery. Drug Deliv Transl Res. 2016;6(6):648–659.
  • Saenger W, Jacob J, Gessler K, et al. Structures of the common cyclodextrins and their larger analogues beyond the doughnut. Chem Rev. 1998;98(5):1787–1802.
  • Hapiot F, Tilloy S, Monflier E. Cyclodextrins as supramolecular hosts for organometallic complexes. Chem Rev. 2006;106(3):767–781.
  • Soliman O-AE-A, Mohamed EAM, El-Dahan MS, et al. Potential use of cyclodextrin complexes for enhanced stability, anti-inflammatory efficacy, and ocular bioavailability of loteprednol etabonate. AAPS PharmSciTech. 2017;18(4):1228–1241.
  • Loftsson T, Hreinsdóttir D, Stefansson E. Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops. J Pharm Pharmacol. 2007;59(5):629–635.
  • Kam JH, Lynch A, Begum R, et al. Topical cyclodextrin reduces amyloid beta and inflammation improving retinal function in ageing mice. Exp Eye Res. 2015;135:59–66.
  • Algar WR, Tavares AJ, Krull UJ. Beyond labels: a review of the application of quantum dots as integrated components of assays, bioprobes, and biosensors utilizing optical transduction. Anal Chim Acta. 2010;673(1):1–25.
  • Pathak S, Cao E, Davidson MC, et al. Quantum dot applications to neuroscience: new tools for probing neurons and glia. J Neurosci. 2006;26(7):1893–1895.
  • Pollinger K, Hennig R, Ohlmann A, et al. Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application. Proc Nat Acad Sci. 2013;110(15):6115–6120.
  • Olson JL, Velez-Montoya R, Mandava N, et al. Intravitreal silicon-based quantum dots as neuroprotective factors in a model of retinal photoreceptor degeneration. Invest Ophthalmol Vis Sci. 2012;53(9):5713–5721.
  • Savla R, Taratula O, Garbuzenko O, et al. Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer. J Control Release. 2011;153(1):16–22.
  • Amato R, Giannaccini M, Dal Monte M, et al. Association of the somatostatin analog octreotide with magnetic nanoparticles for intraocular delivery: a possible approach for the treatment of diabetic retinopathy. Front Bioeng Biotechnol. 2020;8:144.
  • Rong X, Ji Y, Zhu X, et al. Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats. Int J Nanomedicine. 2019;14:45–55.
  • Zeng L, Ma W, Shi L, et al. Poly (lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy. Int J Nanomedicine. 2019;14:6357–6369.
  • Qiu F, Meng T, Chen Q, et al. Fenofibrate-loaded biodegradable nanoparticles for the treatment of experimental diabetic retinopathy and neovascular age-related macular degeneration. Mol Pharm. 2019;16(5):1958–1970.
  • Shoval A, Markus A, Zhou Z, et al. Anti‐VEGF‐aptamer modified C‐dots—A hybrid nanocomposite for topical treatment of ocular vascular disorders. Small. 2019;15(40):1–10.
  • Mahaling B, Srinivasarao DA, Raghu G, et al. A non-invasive nanoparticle mediated delivery of triamcinolone acetonide ameliorates diabetic retinopathy in rats. Nanoscale. 2018;10(35):16485–16498.
  • Gote V, Sikder S, Sicotte J, et al. Ocular drug delivery: present innovations and future challenges. J Pharmacol Exp Ther. 2019;370(3):602–624.
  • Thakur Singh RR, Tekko I, McAvoy K, et al. Minimally invasive microneedles for ocular drug delivery. Expert Opin Drug Deliv. 2017;14(4):525–537.
  • Bian F, Shin CS, Wang C, et al. Dexamethasone drug eluting nanowafers control inflammation in alkali-burned corneas associated with dry eye. Invest Ophthalmol Vis Sci. 2016;57(7):3222–3230.
  • Yuan X, Marcano DC, Shin CS, et al. Ocular drug delivery nanowafer with enhanced therapeutic efficacy. ACS Nano. 2015;9(2):1749–1758.
  • Stahel M, Becker M, Graf N, et al. Systemic interleukin 1β inhibition in proliferative diabetic retinopathy: a prospective open-label study using canakinumab. Retina (Philadelphia, Pa). 2016;36(2):385–391.
  • Scott IU, Jackson GR, Quillen DA, et al. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non–high-risk proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2014;132(5):535–543.
  • Pakzad-Vaezi K, Albiani DA, Kirker AW, et al. A randomized study comparing the efficacy of bevacizumab and ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy. Ophthalmic Surg Lasers Imag Retina. 2014;45(6):521–524.
  • Virgili G, Menchini F, Casazza G, et al. Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy. Cochrane Database Syst Rev. 2015;1:1–18.
  • Carrasco E, Hernández C, Miralles A, et al. Lower somatostatin expression is an early event in diabetic retinopathy and is associated with retinal neurodegeneration. Diabetes Care. 2007;30(11):2902–2908.
  • Leske MC, Wu S-Y, Hennis A, et al. Hyperglycemia, blood pressure, and the 9-year incidence of diabetic retinopathy: the Barbados eye studies. Ophthalmology. 2005;112(5):799–805.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.