Skip to main content
SpringerLink
Log in

Nanotoxicity of Nanobiomaterials in Ocular System and Its Evaluation

  • Chapter
  • First Online:
Book cover Nano-Biomaterials For Ophthalmic Drug Delivery

Abstract

Nanotoxicology is an emerging science under the tremendously growing field of nanotechnology. The unique advantageous properties of nanoparticles or nanobiomaterials have become a challenging issue of primary concern in terms of possible unpredictable toxic interactions of these nanoparticles with the biomolecules in the physiological system. The scanty in vivo studies are insufficient to advocate the therapeutic success stories of nanobiomaterials. A plethora of reports demonstrated only in vitro studies of nanotoxicity assessment. This chapter discusses toxicity issues related to nanobiomaterials targeted for ocular delivery and current methodologies used to assess nanomaterial toxicity along with the challenges and limitations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abdelbary G (2011) Ocular ciprofloxacin hydrochloride mucoadhesive chitosan-coated liposomes. Pharm Dev Technol 16(1):44–56. doi:10.3109/10837450903479988

    Article  CAS  PubMed  Google Scholar 

  2. Abrishami M, Ganavati SZ, Soroush D, Rouhbakhsh M, Jaafari MR, Malaekeh-Nikouei B (2009) Preparation, characterization, and in vivo evaluation of nanoliposomes-encapsulated bevacizumab (avastin) for intravitreal administration. Retina 29(5):699–703

    Article  PubMed  Google Scholar 

  3. Aksungur P, Demirbilek M, Denkbas EB, Vandervoort J, Ludwig A, Unlu N (2011) Development and characterization of Cyclosporine A loaded nanoparticles for ocular drug delivery: cellular toxicity, uptake, and kinetic studies. J Control Release 151(3):286–294. doi:10.1016/j.jconrel.2011.01.010

    Article  CAS  PubMed  Google Scholar 

  4. Al-Halafi AM (2014) Nanocarriers of nanotechnology in retinal diseases. Saudi J Opthalmol. doi:10.1016/j.sjopt.2014.02.009

    Google Scholar 

  5. Al-Nasiry S, Geusens N, Hanssens M, Luyten C, Pijnenborg R. The use of Alamar Blue assay for quantitative analysis of viability, migration and invasion of choriocarcinoma cells. (0268–1161 (Print))

    Google Scholar 

  6. Aljandali A, Pollack H, Yeldandi A, Li Y, Weitzman SA, Kamp DW (2001) Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals. J Lab Clin Med 137:330–339

    Article  CAS  PubMed  Google Scholar 

  7. Alonso MJ, Sánchez A (2003) The potential of chitosan in ocular drug delivery. J Pharm Pharmacol 55:1451–1463

    Article  CAS  PubMed  Google Scholar 

  8. Amo EMd, Urtti A (2008) Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today 13(3–4):135–143

    PubMed  Google Scholar 

  9. Aubry JP, Blaecke A, Lecoanet-Henchoz S, Jeannin P, Herbault N, Caron G, … Bonnefoy JY (1999) Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity. Cytometry 37:197–204

    Google Scholar 

  10. Azevedo Costa CL, Chaves IS, Ventura-Lima J, Ferreira JLR, Ferraz L, de Carvalho LM, Monserrat JM (2012) In vitro evaluation of co-exposure of arsenium and an organic nanomaterial (fullerene, C60) in zebrafish hepatocytes. Comp Biochem Physiol C Toxicol Pharmacol 155(2):206–212. doi:10.1016/j.cbpc.2011.08.005

    Article  CAS  PubMed  Google Scholar 

  11. Bartkowiak D, Hogner S, Baust H, Nothdurft W, Rottinger EM (1999) Comparative analysis of apoptosis in HL60 detected by annexin-V and fluorescein diacetate. Cytometry 37:191–196

    Article  CAS  PubMed  Google Scholar 

  12. Bejjani RA, BenEzra D, Cohen H, Rieger J, Andrieu C, Jeaanny JC, … Behar-Cohen FF (2005) Nanoparticles for gene delivery to retinal pigment epithelial cells. Mol Vis 11:124–132

    Google Scholar 

  13. Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11:127–152

    Article  CAS  PubMed  Google Scholar 

  14. Borenfreund E, Puerner JA (1985) Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 24:119–124

    Article  CAS  PubMed  Google Scholar 

  15. Bottini M, Bruckner S, Nika K, Bottini N, Bellucci S, Magrini A et al (2006) Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett 160:121–126

    Article  CAS  PubMed  Google Scholar 

  16. Bourges JL, Gautier SE, Delie F, Bejjani RA, Jeanny JC, Gurny R, … Behar-Cohen FF (2003) Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Investig Ophthalmol Vis Sci 44:3562–3569

    Google Scholar 

  17. Braydich-Stolle L, Hussain SM, Schlager J, Hofmann MC (2005) In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 88:412–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Browning LM, Kerry J, Lee KJ, Huang T, Nallathamby PD, Lowman JE, Xu NXH (2009) Random walk of single gold nanoparticles in zebrafish embryos leading to stochastic toxic effects on embryonic developments. Nanoscale 1:138–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52(0076–6879 (Print)):302–310

    Google Scholar 

  20. Calvo P, Sánchez A, Martínez J, López MI, Calonge M, Pastor JC, Alonso MJ (1996) Polyester nanocapsules as new topical ocular delivery systems for cyclosporin A. Pharm Res 13:311–315

    Article  CAS  PubMed  Google Scholar 

  21. Cardillo JA, Oliveira AAS-F AG (2006) Intravitreal bioerudivel sustained-release triamcinolone microspheres system (RETAAC). Preliminary report of its potential usefulnes for the treatment of diabetic macular edema. Arch Soc Esp Oftalmol 81(12). doi:10.4321/S0365-66912006001200002

  22. Chan WH, Shiao NH (2008) Cytotoxic effect of CdSe quantum dots on mouse embryonic development. Acta Pharmacol Sin 29:259–266

    Article  CAS  PubMed  Google Scholar 

  23. Chan WH, Shiao NH, Lu PZ (2006) CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. Toxicol Lett 167:191–200

    Article  CAS  PubMed  Google Scholar 

  24. Cheng J, Flahaut E, Cheng S (2007) Effect of carbon nanotubes on developing zebrafish (Danio rerio) embryos. Environ Toxicol Chem 26:708–716

    Article  CAS  PubMed  Google Scholar 

  25. Choi J, Wang NS (2011) Nanoparticles in biomedical applications and their safety concerns. In: Fazel R (ed) Biomedical engineering – from theory to applications. 51000 Rijeka, Croatia- European Union. InTech, pp 300–314

    Google Scholar 

  26. Chou CC, Hsiao HY, Hong QS, Chen CH, Peng YW, Chen HW et al (2008) Single-walled carbon nanotubes can induce pulmonary injury in mouse model. Nano Lett 8:437–445

    Article  CAS  PubMed  Google Scholar 

  27. Civiale C, Licciardi M, Cavallaro G, Giammona G, Mazzone MG (2009) Polyhydroxyethylaspartamide-based micelles for ocular drug delivery. Int J Pharm 378(1–2):177–186. doi:10.1016/j.ijpharm.2009.05.028

    Article  CAS  PubMed  Google Scholar 

  28. European Commission (2004) Methods for the determination of physico-chemical properties, toxicity and ecotoxicity. B-1049 Brussels. European Commission

    Google Scholar 

  29. Cui DX (2005) Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 155:73–85

    Article  CAS  PubMed  Google Scholar 

  30. Davoren M, Herzog E, Casey A, Cottineau B, Chambers G, Byrne HJ, Lyng FM (2007) In vitro toxicity evaluation of single walled carbon nanotubes on human A549 lung cells. Toxicol In Vitro 21:438–448

    Article  CAS  PubMed  Google Scholar 

  31. Desai N (2012) Challenges in development of nanoparticle-based therapeutics. AAPS J 14(2):282–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Deshpande A, Narayanan K, Lehnert BE (2002) Silica-induced generation of extracellular factor(s) increases reactive oxygen species in human bronchial epithelial cells. Toxicol Sci 67:275–283

    Article  CAS  PubMed  Google Scholar 

  33. Di Tommaso C, Torriglia A, Furrer P, Behar-Cohen F, Gurny R, Möller M (2011) Ocular biocompatibility of novel Cyclosporin A formulations based on methoxy poly(ethylene glycol)-hexylsubstituted poly(lactide) micelle carriers. Int J Pharm 416(2):515–524. doi:10.1016/j.ijpharm.2011.01.004

    Article  PubMed  CAS  Google Scholar 

  34. Diebold Y, Clonge M (2010) Applications of nanoparticles in ophthalmology. Prog Retin Eye Res 29:596–609

    Article  CAS  PubMed  Google Scholar 

  35. Duffin R, Tran L, Brown D, Stone V, Donaldson K (2007) Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 19:849–856

    Article  CAS  PubMed  Google Scholar 

  36. ECVAM (1997) Statement on the scientific validity of the 3T3 NRU PT test (an in vitro test for phototoxic potential). European Centre for the Validation of Alternative Methods. JRC Environment Institute 21020 Ispra (VA) Italy

    Google Scholar 

  37. Edwards A, Prausnitz MR (2001) Predicted permeability of the corneal to topical drugs. Pharm Res 18:1497–1508

    Article  CAS  Google Scholar 

  38. Engeland M v, Nieland LJW, Ramaekers FCS, Schutte B, Rtelingsperger CPM (1998) Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31:1–9

    Article  PubMed  Google Scholar 

  39. Espuelas MMMS, Mirshahi M, Arnedo A, Irache JM (2002) Efficacy of ganciclovir-loaded nanoparticles in human cytomegalovirus (HCMV)-infected cells. J Drug Target 10:231–238

    Article  PubMed  CAS  Google Scholar 

  40. Filion MC, Phillips NC (1998) Major limitations in the use of cationic liposomes for DNA delivery. Int J Pharm 162:159–170

    Article  CAS  Google Scholar 

  41. Firme Iii CP, Bandaru PR (2010) Toxicity issues in the application of carbon nanotubes to biological systems. Nanomedicine 6(2):245–256. doi:10.1016/j.nano.2009.07.003

    Google Scholar 

  42. Fujii NKS (2011) Recent advances in ocular drug delivery systems. Polymers 3:193–221

    Article  CAS  Google Scholar 

  43. Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation (0021–9525 (Print))

    Google Scholar 

  44. Ghaderi S, Ramesh B, Seifalian AM (2011) Fluorescence nanoparticles “quantum dots” as drug delivery system and their toxicity: a review. J Drug Target 19(7):475–486

    Article  CAS  PubMed  Google Scholar 

  45. Gilmour PS, Brown DM, Beswick PH, MacNee W, Rahman I, Donaldson K (1997) Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors. Environ Health Perspect 105(Suppl 5):1313–1317

    Google Scholar 

  46. Gonzalez-Mira E, Egea MA, Garcia ML, Souto EB (2010) Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC. Colloids Surf B Biointerfaces 81(2):412–421. doi:10.1016/j.colsurfb.2010.07.029

    Article  CAS  PubMed  Google Scholar 

  47. Goodman CM, McCusker CD, Yilmaz T, Rotello VM (2004) Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 15:897–900

    Article  CAS  PubMed  Google Scholar 

  48. Griffitt R, Weil R, Hyndman K, Denslow N, Powers K, Taylor D, Barber D (2007) Exposure to copper nanoparticles causes gill injury and acute lethality in zebrafish (Danio rerio). Environ Sci Technol 41:8178–8186

    Article  CAS  PubMed  Google Scholar 

  49. Guđmundsdóttir E, Stefánsson E, Bjarnadóttir G, Sigurjónsdóttir JF, Guđmundsdóttir G, Masson M, Loftsson T (2000) Methazolamide 1 % in cyclodextrin solution lowers IOP in human ocular hypertension. Invest Ophthalmol Vis Sci 41(11):3552–3554

    PubMed  Google Scholar 

  50. Gupta H, Aqil M, Khar RK, Ali A, Bhatnagar A, Mittal G (2010) Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery. Nanomedicine 6(2):324–333. doi:10.1016/j.nano.2009.10.004

    CAS  PubMed  Google Scholar 

  51. Habib FS, Fouad EA, Abdel-Rhaman MS, Fathalla D (2010) Liposomes as an ocular delivery system of fluconazole: in-vitro studies. Acta Ophthalmol (Copenh) 88(8):901–904. doi:10.1111/j.1755-3768.2009.01584.x

    Article  CAS  Google Scholar 

  52. Hämäläinen KM, Kananen K, Auriola S, Kontturi K, Urtti A (1997) Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci 38:627–634

    PubMed  Google Scholar 

  53. Han SG, Andrews R, Gairola C, Bhalla DK (2008) Acute pulmonary effects of combined exposure to carbon nanotubes and ozone in mice. Inhal Toxicol 20:391–398

    Article  CAS  PubMed  Google Scholar 

  54. Harhaji L, Isakovic A, Vucicevic L, Janjetovic K, Misirkic M, Markovic Z, … Trajkovic V (2007) Modulation of tumor necrosis factor-mediated cell death by fullerenes. Pharm Res 25:1365–1376

    Google Scholar 

  55. Heiden T, Dengler E, Kao W, Heideman W, Peterson R (2007) Developmental toxicity of low generation PAMAM dendrimers in zebrafish. Toxicol Appl Pharmacol 225:70–79

    Google Scholar 

  56. Hempel SL, Buettner GR, O’Malley YQ, Wessels DA, Flaherty DM (1999) Dihydrofluorescein diacetate is superior for detecting intracellular oxidants: comparison with 20,70-dichlorodihydrofluorescein diacetate, 5(and 6)- carboxy-20,70 dichlorodihydrofluorescein diacetate, and dihydrorhodamine 123. Free Radic Biol Med 27:146–159

    Article  CAS  PubMed  Google Scholar 

  57. Hillyer JF, Albrecht RM (2001) Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci 90:1927–1936

    Article  CAS  PubMed  Google Scholar 

  58. Huang M, Khor E, Lim LY (2004) Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm Res 21:344–353

    Article  CAS  PubMed  Google Scholar 

  59. Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975–983

    Article  CAS  PubMed  Google Scholar 

  60. Isakovic A, Markovic Z, Todorovic-Markovic B, Nikolic N, Vranjes-Djuric S, Mirkovic M, … Trajkovic V (2006) Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol Sci 91:173–183

    Google Scholar 

  61. Jackson BP, Bugge D, Ranville JF, Chen CY (2012) Bioavailability, toxicity, and bioaccumulation of quantum dot nanoparticles to the amphipod Leptocheirus plumulosus. Environ Sci Technol 46(10):5550–5556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Jacobsen NR, Moller P, Jensen KA, Vogel U, Ladefogel O, Loft S et al (2009) Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE−/− mice. Toxicology 6:1–17

    Google Scholar 

  63. Jakubowski W, Bartosz G (2000) 2,7-Dichlorofluorescin oxidation and reactive oxygen species: what does it measure? Cell Biol Int 24:757–760

    Article  CAS  PubMed  Google Scholar 

  64. Jeng HA, Swanson J (2006) Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health A Tox Hazard Subst Environ Eng 41:2699–2711

    Article  CAS  PubMed  Google Scholar 

  65. Jia G (2005) Cytotoxicity of carbon nanomaterials: single-wall nanotube, multiwall nanotube, and fullerene. Environ Sci Technol 39:1378–1383

    Article  CAS  PubMed  Google Scholar 

  66. Jong WHD, Borm P (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 3:133–149

    Article  PubMed  PubMed Central  Google Scholar 

  67. Juberías JR, Calonge M, Gómez S, López MI, Calvo P, Herreras JM, Alonso MJ (1998) Efficacy of topical cyclosporine-loaded nanocapsules on keratoplasty rejection model in the rat. Curr Eye Res 17:39–46

    Article  PubMed  Google Scholar 

  68. Kalbacova M, Kalbac M, Dunsch L, Kataura H, Hempel U (2006) The study of the interaction of human mesenchymal stem cells and monocytes/macrophages with single-walled carbon nanotube films. Phys Status Solidi B 243:3514–3518

    Article  CAS  Google Scholar 

  69. Kapadia MR, Chow LW, Tsihlis ND, Ahanchi SS, Eng JW, Murar J, … Kibbe MR (2008) Nitric oxide and nanotechnology: a novel approach to inhibit neointimal hyperplasia. J Vasc Surg 47(1):173–182

    Google Scholar 

  70. Kassem MA, AbdelRahman AA, Ghorab MM, Ahmed MB, Khalil RM (2007) Nanosuspensions as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm 340:126–133

    Article  CAS  PubMed  Google Scholar 

  71. Kaur IP, Garg A, Singla AK, Aggarwal D (2004) Vesicular systems in ocular drug delivery: an overview. Int J Pharm 269:1–14

    Article  CAS  PubMed  Google Scholar 

  72. Kaur IP, Kanwar M (2002) Ocular preparations: the formulation approach. Drug Dev Ind Pharm 28:473–493

    Article  CAS  PubMed  Google Scholar 

  73. Kayat J, Gajbhiye V, Tekade RK, Jain NK (2011) Pulmonary toxicity of carbon nanotubes: a systematic report. Nanomedicine 7(1):40–49. doi:10.1016/j.nano.2010.06.008

    CAS  PubMed  Google Scholar 

  74. Keane RW, Srinivasan A, Foster LM, Testa M-P, Örd T, Nonner D, … Kayalar C (1997) Activation of CPP32 during apoptosis of neurons and astrocytes. J Neurosci Res 48(2):168–180. doi:10.1002/(sici)1097-4547(19970415)48:2<168::aid-jnr9>3.0.co;2-a

  75. Keister JC, Cooper ER, Missel PJ, Lang JC, Hager DF (1991) Limits on optimizing ocular drug delivery. J Pharm Sci 80:50–53

    Article  CAS  PubMed  Google Scholar 

  76. King Heiden TC, Dengler E, Kao WJ, Heideman W, Peterson RE (2007) Developmental toxicity of low generation PAMAM dendrimers in zebrafish. Toxicol Appl Pharmacol 225(1):70–79. doi:10.1016/j.taap.2007.07.009

    Article  CAS  Google Scholar 

  77. Koh JY, Choi DW (1987) Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods 20:83–90

    Article  CAS  PubMed  Google Scholar 

  78. Kompella UB, Amrite AC, Ravi RP, Durazo SA (2013) Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res 36:172–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, Oers MH (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84:1415–1420

    CAS  PubMed  Google Scholar 

  80. Korzeniewski C, Callewaert DM (1983) An enzyme-release assay for natural cytotoxicity. J Immunol Methods 64:313

    Article  CAS  PubMed  Google Scholar 

  81. Lam CW, James JT, McCluskey R, Hunter RL (2004) Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126–134

    Article  CAS  PubMed  Google Scholar 

  82. Langer K, Zimmer A, Kreuter J (1997) Acrylic nanoparticles for ocular drug delivery. S.T.P Pharm Sci 7(6): 445–451

    Google Scholar 

  83. Lee JK, Kim DB, Kim JI, Kim PY (2000) In vitro cytotoxicity tests on cultured human skin fibroblasts to predict skin irritation potential of surfactants. Toxicol In Vitro 14:345–349

    Google Scholar 

  84. Lequin RM (2005) Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin Chem 51:2415–2418

    Article  CAS  PubMed  Google Scholar 

  85. Li JJ, Zou L, Hartano D, Ong CN, Bay BH, Yung LYL (2008) Gold nanoparticles induce oxidative damage in lung fibroblasts in vitro. Adv Mater 20:138–142

    Article  CAS  Google Scholar 

  86. Lison D, Thomassen LC, Rabolli V, Gonzalez L, Napierska D, Seo JW, … Martens JA (2008) Nominal and effective dosimetry of silica nanoparticles in cytotoxicity assays. Toxicol Sci 104:155–162

    Google Scholar 

  87. Liu M, Fréchet JMJ (1999) Designing dendrimers for drug delivery. Pharm Sci Technol Today 2(10):393–401. doi:10.1016/s1461-5347(99)00203-5

    Article  CAS  PubMed  Google Scholar 

  88. Losa C, Marchal-Heussler L, Orallo F, Vila-Jato JL, Alonso MJ (1993) Design of new formulations for topical ocular administration: polymeric nanocapsules containing metipranolol. Pharm Res 10:80–87

    Article  CAS  PubMed  Google Scholar 

  89. M, MP, Yin XJ, Zhao J, Ding M, Leonard S, Schwegler-Berry D, et al (2008) Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 116:1211–1217

    Google Scholar 

  90. Maeda R, Noiri E, Isobe H, Homma T, Tanaka T, Negishi K, … Nakamura E (2008) A water-soluble fullerene vesicle alleviates angiotensin II-induced oxidative stress in human umbilical venous endothelial cells. Hypertens Res 31:141–151

    Google Scholar 

  91. Magrez A (2006) Cellular toxicity of carbon-based nanomaterials. Nano Lett 6:1121–1125

    Article  CAS  PubMed  Google Scholar 

  92. Mannermaa E, Vellonen KS, Urtti A (2006) Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev 58:1136–1163

    Article  CAS  PubMed  Google Scholar 

  93. Maynard AD, Aitken JR, Butz T, Colvin V, Donaldson K, Oberdörster G et al (2006) Safe handling of nanotechnology. Nature 444:267–269

    Article  CAS  PubMed  Google Scholar 

  94. Mehanna MM, Elmaradny HA, Samaha MW (2010) Mucoadhesive liposomes as ocular delivery system: physical, microbiological, and in vivo assessment. Drug Dev Ind Pharm 36(1):108–118. doi:10.3109/03639040903099751

    Article  CAS  PubMed  Google Scholar 

  95. Merodio M, Arnedo A, Renedo MJ, Irache JM (2001) Ganciclovir-loaded nanoparticles: characterization and in vitro release properties. Eur J Pharm Sci 12:251–259

    Article  CAS  PubMed  Google Scholar 

  96. Monteiro-Riviere NA, Inman AO (2006) Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 44:1070–1078

    Article  CAS  Google Scholar 

  97. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  98. Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK (2008) Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimisation and in vitro characterisation. Eur J Pharm Biopharm 68:513–525

    CAS  PubMed  Google Scholar 

  99. Mukherjee SP, Davoren M, Byrne HJ (2010) In vitro mammalian cytotoxicological study of PAMAM dendrimers – towards quantitative structure activity relationships. Toxicol In Vitro 24(1):169–177. doi:10.1016/j.tiv.2009.09.014

    Article  CAS  PubMed  Google Scholar 

  100. Mukherjee SP, Lyng FM, Garcia A, Davoren M, Byrne HJ (2010) Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in mammalian cells. Toxicol Appl Pharmacol 248(3):259–268. doi:10.1016/j.taap.2010.08.016

    Article  CAS  PubMed  Google Scholar 

  101. Muller J, Huauxa F, Moreaub N, Missona P, Heiliera JF, Delosc M et al (2005) Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 207:221–231

    Article  CAS  PubMed  Google Scholar 

  102. Nachlas MM, Margulies SI, Goldberg JD, Seligman AM (1960) The determination of lactic dehydrogenase with a tetrazolium salt. Anal Biochem 1:317

    Article  CAS  PubMed  Google Scholar 

  103. Nagarwal RC, Kant S, Singh PN, Maiti P, Pandit JK (2009) Polymeric nanoparticulate system: a potential approach for ocular drug delivery. J Control Release 136:2–13

    Article  CAS  PubMed  Google Scholar 

  104. Naha PC, Davoren M, Lyng FM, Byrne HJ (2010) Reactive oxygen species (ROS) induced cytokine production and cytotoxicity of PAMAM dendrimers in J774A.1 cells. Toxicol Appl Pharmacol 246(1–2):91–99. doi:10.1016/j.taap.2010.04.014

    Article  CAS  PubMed  Google Scholar 

  105. Nemes Z, Dietz R, Lüth JB, Gomba S, Hackenthal E, Gross F (1979) The pharmacological relevance of vital staining with neutral red. Cell Mol Life Sci 35:1475

    Article  CAS  Google Scholar 

  106. Normand N, Valamanesh F, Savoldelli M, Mascarelli F, BenEzra D, Courtois Y, Behar-Cohen FF (2005) VP22 light controlled delivery of oligonucleotides to ocular cells in vitro and in vivo. Mol Vis 11:184–191

    CAS  PubMed  Google Scholar 

  107. Jacobsen NR, Pojana G, White P, Moller P, Cohn CA, Korsholm KS, et al (2008) Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C60 fullerenes in the FE1-Muta mouse lung epithelial cells. Environ Mol Mutagen 49:476–487

    Google Scholar 

  108. Pan Y, Neuss S, Leifert A, Fischler M, Wen F, Simon U, … Jahnen-Dechent W (2007) Size-dependent cytotoxicity of gold nanoparticles. Small 3:1941–1949

    Google Scholar 

  109. Paolicelli P, Fuente M d l, Sánchez A, Seijo B, Alonso MJ (2009) Chitosan nanoparticles for drug delivery to the eye. Expert Opin Drug Deliv 6:239–253

    Article  CAS  PubMed  Google Scholar 

  110. Parkinson TM, Ferguson E, Febbraro S, Bakhtyari A, King M, Mundasad M (2003) Tolerance of ocular iontophoresis in healthy volunteers. J Ocul Pharmacol Ther 19(2):145–151. doi:10.1089/108076803321637672

    Article  CAS  PubMed  Google Scholar 

  111. Peng J, He X, Wang K, Tan W, Li H, Xing X, Wang Y (2006) An antisense oligonucleotide carrier based on amino silica nanoparticles for antisense inhibition of cancer cells. Nanomedicine 2:113–120

    CAS  PubMed  Google Scholar 

  112. Pepić I, Hafner A, Lovrić J, Pirkić B, Filipović-Grčić J (2010) A nonionic surfactant/chitosan micelle system in an innovative eye drop formulation. J Pharm Sci 99(10):4317–4325. doi:10.1002/jps.22137

    Article  PubMed  CAS  Google Scholar 

  113. Pernodet N, Fang X, Sun Y, Bakhtina A, Ramakrishnan A, Sokolov J, … Rafailovich M (2006) Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. Small 2:766–773

    Google Scholar 

  114. Petit A-N, Eullaffroy P, Debenest T, Gagné F (2010) Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii. Aquat Toxicol 100(2):187–193. doi:10.1016/j.aquatox.2010.01.019

    Article  CAS  PubMed  Google Scholar 

  115. Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G (2002) Eudragit RS100 nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci 16:53–61

    Article  CAS  PubMed  Google Scholar 

  116. Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A et al (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3:423–428

    Article  CAS  PubMed  Google Scholar 

  117. Puck TT, Marcus PI (1956) Action of X-rays on mammalian cells. J Exp Med 103(5):653–666. doi:10.1084/jem.103.5.653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Pulskamp K, Diabate S, Krug HF (2007) Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicol Lett 168:58–74

    Article  CAS  PubMed  Google Scholar 

  119. Rafie F, Javadzadeh Y, Javadzadeh AR, Ghavidel LA, Jafari B, Moogooee M, Davaran S (2010) In vivo evaluation of novel nanoparticles containing dexamethasone for ocular drug delivery on rabbit eye. Curr Eye Res 35(12):1081–1089. doi:10.3109/02713683.2010.508867

    Article  CAS  PubMed  Google Scholar 

  120. Ramires PA, Romito A, Cosentino F, Milell E (2001) The influence of titania/hydroxyapatite composite coatings on in vitro osteoblasts behaviour. Biomaterials 22:1467–1474

    Article  CAS  PubMed  Google Scholar 

  121. Rao KM, Porter DW, Meighan T, Castranova V (2004) The sources of inflammatory mediators in the lung after silica exposure. Environ Health Perspect 112:1679–1686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Roberts JE, Wielgus AR, Boyes WK, Andley U, Chignell CF (2008) Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells. Toxicol Appl Pharmacol 228:49–58

    Article  CAS  PubMed  Google Scholar 

  123. Robledo RF, Buder-Hoffmann SA, Cummins AB, Walsh ES, Taatjes DJ, Mossman BT (2000) Increased phosphorylated extracellular signal-regulated kinase immunoreactivity associated with proliferative and morphologic lung alterations after chrysotile asbestos inhalation in mice. Am J Pathol (0002–9440 (Print)). 156(4):1307–1316.

    Google Scholar 

  124. Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA (2007) Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes. J Invest Dermatol 127:143–153

    Article  CAS  PubMed  Google Scholar 

  125. Sadaf A, Zeshan B, Wang Z, Zhang R, Xu S, Wang C, Cui Y (2012) Toxicity evaluation of hydrophilic CdTe quantum dots and CdTe@SiO2 nanoparticles in mice. J Nanosci Nanotechnol 12(11):8287–8292

    Google Scholar 

  126. Sahoo SK, Dilnawaza F, Krishnakumar S (2008) Nanotechnology in ocular drug delivery. Drug Discov Today 13(3–4):144–151

    Article  CAS  PubMed  Google Scholar 

  127. Sakai T, Kohno H, Higaki TIM, Saito S, Matsushima M, Mizushima Y, Kitahara K (2006) Treatment of experimental autoimmune uveoretinitis with poly(lactic acid) nanoparticles encapsulating betamethasone phosphate. Exp Eye Res 82:657–663

    Article  CAS  PubMed  Google Scholar 

  128. Sasaki H, Yamamura K, Mukai T, Nishida K, Nakamura J, Nakashima M, Ichikawam M (1999) Enhancement of ocular drug penetration. Crit Rev Ther Drug Carrier Syst 16:85–146

    Article  CAS  PubMed  Google Scholar 

  129. Sayes CM, Fortner JD, Guo W, Lyon D, Boyd AM, Ausman KD, … Colvin VL (2004) The differential cytotoxicity of water-soluble fullerenes. Nano Lett 4(10):1881–1887. doi:10.1021/nl0489586

    Google Scholar 

  130. Sayes CM, Gobin AM, Ausman KD, Mendez J, West JL, Colvin VL (2005) Nano-C60 cytotoxicity is due to lipid peroxidation. Biomaterials 26(36):7587–7595. doi:10.1016/j.biomaterials.2005.05.027

    Article  CAS  PubMed  Google Scholar 

  131. Sayes CM, Marchione AA, Reed KL, Warheit DB (2007) Comparative pulmonary toxicity assessments of C60 water suspensions in rats: few differences in fullerene toxicity in vivo in contrast to in vitro profiles. Nano Lett 7:2399–2406

    Article  CAS  PubMed  Google Scholar 

  132. Sayes CM, Reed KL, Warheit DB (2007) Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci 97:163–180

    Article  CAS  PubMed  Google Scholar 

  133. Schins RP, Duffin R, Hohr D, Knaapen AM, Shi T, Weishaupt C, Stone V, … Borm PJ (2002) Surface modification of quartz inhibits toxicity, particle uptake, and oxidative DNA damage in human lung epithelial cells. Chem Res Toxicol 15(9):1116–1173

    Google Scholar 

  134. Schoenwald RD (1990) Ocular drug delivery: pharmacokinetics considerations. Clin Pharmacokinet 18:255–269

    Article  CAS  PubMed  Google Scholar 

  135. Shafie MAA, Fayek HHM (2013) Formulation and evaluation of betamethasone sodium phosphate loaded nanoparticles for ophthalmic delivery. J Clin Exp Ophthalmol 4:273. doi:10.4172/2155-9570.1000273

    Google Scholar 

  136. Sharma A, Tandon A, Tovey JCK, Gupta R, Robertson JD, Fortune JA, … Mohan RR (2011) Polyethylenimine-conjugated gold nanoparticles: gene transfer potential and low toxicity in the cornea. Nanomedicine: Nanotechnol Biol Med 7(4):505–513

    Google Scholar 

  137. Shen B, Scaiano JC, English AM (2006) Zeolite encapsulation decreases TiO2- photosensitized ROS generation in cultured human skin fibroblasts. Photochem Photobiol 82:5–12

    Article  CAS  PubMed  Google Scholar 

  138. Shvedova AA (2008) Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol 295:552–565

    Article  CAS  Google Scholar 

  139. Shvedova AA, Castranova V, Kisin KR, Schwegler-Berry D, Murray AR, Gandelsman VZ (2003) Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A 66:1909–1926

    Article  CAS  PubMed  Google Scholar 

  140. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. (0014–4827 (Print))

    Google Scholar 

  141. Singh S, Shi T, Duffin R, Albrecht C, van Berlo D, Höhr D, … Schins RPF (2007) Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO2: role of the specific surface area and of surface methylation of the particles. Toxicol Appl Pharmacol 222(2):141–151. doi:10.1016/j.taap.2007.05.001

    Google Scholar 

  142. Slater TF, Sawyer B, Straeuli U (1963) Studies on succinate-tetrazolium reductase systems. III. Points of coupling of four different tetrazolium salts. Biochim Biophys Acta 77:383–393

    Article  CAS  PubMed  Google Scholar 

  143. Smart SK, Cassady A, Lu GQ, Martin DJ (2006) The biocompatibility of carbon nanotubes. Carbon 44:1034–1047

    Article  CAS  Google Scholar 

  144. Spataro G, Malecaze F, Turrin C-O, Soler V, Duhayon C, Elena P-P, … Caminade A-M (2010) Designing dendrimers for ocular drug delivery. Eur J Med Chem 45(1):326–334. doi:10.1016/j.ejmech.2009.10.017

    Google Scholar 

  145. Spielmann H, Hoffmann S, Liebsch M, Botham P, Fentem JH, Eskes C, … Zuang V (2007) The ECVAM international validation study on in vitro tests for acute skin irritation: report on the validity of the EPISKIN and EpiDerm assays and on the Skin Integrity Function Test. Altern Lab Anim 35:559–601

    Google Scholar 

  146. Srinivasula SM, Saleh A, Ahmad M, Fernandes-Alnemri T, Alnemri ES (2001) Isolation and assay of caspases. Methods Cell Biol 66:1–27

    Article  CAS  PubMed  Google Scholar 

  147. Stoker E, Purser F, Kwon S, Park YB, Lee JS (2008) Alternative estimation of human exposure of single-walled carbon nanotubes using three-dimensional tissue-engineered human lung. Int J Toxicol 27:441–448

    Article  CAS  PubMed  Google Scholar 

  148. Strober W (2001) Trypan blue exclusion test of cell viability. Curr Protoc Immunol (1934-368X (Electronic))

    Google Scholar 

  149. Tan WB, Zhang Y (2005) Surface modification of gold and quantum dot nanoparticles with chitosan for bioapplications. J Biomed Mater Res A 75:56–62

    Article  PubMed  CAS  Google Scholar 

  150. Tao F, Kobzik L (2002) Lung macrophage-epithelial cell interactions amplify particle-mediated cytokine release. Am J Respir Cell Mol Biol 26:499–505

    Article  CAS  PubMed  Google Scholar 

  151. Tarpey MM, Wink DA, Grisham MB (2004) Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. Am J Physiol Regul Integr Comp Physiol 286:R431–R444

    Google Scholar 

  152. Thibodeau M, Giardina C, Hubbard AK (2003) Silica-induced caspase activation in mouse alveolar macrophages is dependent upon mitochondrial integrity and aspartic proteolysis. Toxicol Sci 76:91–101

    Article  CAS  PubMed  Google Scholar 

  153. Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4:145–160

    Article  CAS  PubMed  Google Scholar 

  154. Trotter PJ, Orchard MA, Walker JH (1995) Ca2+ concentration during binding determines the manner in which annexin V binds to membranes. Biochem J 308(Pt 2):591–598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Ulrich KE, Cannizzaro SM, Langer RS, Shakeshelf KM (1999) Polymeric systems for controlled drug release. Chem Rev 99:3181–3198

    Article  CAS  Google Scholar 

  156. Urtti A (2006) Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 58:1131–1135

    Article  CAS  PubMed  Google Scholar 

  157. Usenko C, Harper S, Tanguay R (2008) Fullerene C60 exposure elicits an oxidative stress response in embryonic zebrafish. Toxicol Appl Pharmacol 229:44–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Vandamme TF, Brobeck L (2005) Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release 102(1):23–38. doi:10.1016/j.jconrel.2004.09.015

    Article  CAS  PubMed  Google Scholar 

  159. Veeranarayanan S, P A, Mohamed MS, Nagaoka Y, Iwai S, Nakagame Y, Kashiwada S, Yoshida Y, Maekawa T, Kumar DS (2012) Synthesis and application of luminescent single CdS quantum dot encapsulated silica nanoparticles directed for precision optical bioimaging. Int J Nanomedicine 7:3769–3786

    Google Scholar 

  160. Vega E, Egea MA, Valls O, Espina M, García ML (2006) Flurbiprofen loaded biodegradable nanoparticles for ophthalmic administration. J Pharm Sci 95:2393–2405

    Article  CAS  PubMed  Google Scholar 

  161. Volotinen M, Mäenpää J, Kautiainen H, Tolonen A, Uusitalo J, Ropo A, … Aine E (2009) Ophthalmic timolol in a hydrogel vehicle leads to minor inter-individual variation in timolol concentration in aqueous humor. Eur J Pharm Sci 36(2–3):292–296. doi:10.1016/j.ejps.2008.10.004

    Google Scholar 

  162. Wagner AJ, Bleckmann CA, Murdock RC, Schrand AM, Schlager JJ, Hussain SM (2007) Cellular interaction of different forms of aluminum nanoparticles in rat alveolar macrophages. J Phys Chem B 111:7353–7359

    Article  CAS  PubMed  Google Scholar 

  163. Wang SG, Lu WT, Tovmachenko O, Rai US, Yu HT, Ray PC (2008) Challenge in understanding size and shape dependent toxicity of gold nanomaterials in human skin keratinocytes. Chem Phys Lett 463:145–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Wilson MR, Stone V, Cullen RT, Searl A, Maynard RL, Donaldson K (2000) In vitro toxicology of respirable Montserrat volcanic ash. Occup Environ Med 57:727–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Worle-Knirsch JM, Pulskamp K, Krug HF (2006) Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 6:1261–1268

    Article  CAS  PubMed  Google Scholar 

  166. Wottrich R, Diabate S, Krug HF (2004) Biological effects of ultrafine model particles in human macrophages and epithelial cells in mono- and co-culture. Int J Hyg Environ Health 207:353–361

    Article  CAS  PubMed  Google Scholar 

  167. Wroblewski F, Ladue JS (1955) Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 90:210–213

    Article  CAS  PubMed  Google Scholar 

  168. Xiong D, Fang T, Yu L, Sima X, Zhu W (2011) Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress and oxidative damage. Sci Total Environ 409(8):1444–1452. doi:10.1016/j.scitotenv.2011.01.015

    Article  CAS  PubMed  Google Scholar 

  169. Xu J, Li X, Sun F (2011) In vitro and in vivo evaluation of ketotifen fumarate-loaded silicone hydrogel contact lenses for ocular drug delivery. Drug Deliv 18(2):150–158. doi:10.3109/10717544.2010.522612

    Article  CAS  PubMed  Google Scholar 

  170. Yacobi NR, Phuleria HC, Demaio L, Liang CH, Peng CA, Sioutas C, … Crandall ED (2007) Nanoparticle effects on rat alveolar epithelial cell monolayer barrier properties. Toxicol In Vitro 21:1373–1381

    Google Scholar 

  171. Yang CF, Shen HM, Shen Y, Zhuang ZX, Ong CN (1997) Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts (MRC-5 cells). Environ Health Perspect 105(7):712–716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Yang XL, Fan CH, Zhu HS (2002) Photo-induced cytotoxicity of malonic acid [C(60)]fullerene derivatives and its mechanism. Toxicol In Vitro 16:41–46

    Article  CAS  PubMed  Google Scholar 

  173. Yao W, Sun K, Mu H, Liang N, Liu Y, Yao C, … Wang A (2010) Preparation and characterization of puerarin-dendrimer complexes as an ocular drug delivery system. Drug Dev Ind Pharm 36(9):1027–1035. doi:10.3109/03639041003610799

    Google Scholar 

  174. Yen HJ, Hsu SH, Tsai CL (2009) Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small 5:1553–1561

    Article  CAS  PubMed  Google Scholar 

  175. Yong K-T, Wang Y, Roy I, Rui H, Swihart MT, Law W-C, … Reynolds JL (2012) Preparation of quantum dot/drug nanoparticle formulations for traceable targeted delivery and therapy. Theranostics 2(7):681–694

    Google Scholar 

  176. Zeni O, Palumbo R, Bernini R, Zeni P, Sarti M, Scarfì MR (2008) Cytotoxicity investigation on cultured human blood cells treated with single-wall carbon nanotubes. Sensors 8:500–519

    Article  Google Scholar 

  177. Zhu X, Zhu L, Duan Z, Qi R, Li Y, Lang Y (2008) Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to zebrafish (Danio rerio) early developmental stage. J Environ Sci Health A Tox Hazard Subst Environ Eng 43:278–284

    Article  CAS  PubMed  Google Scholar 

  178. Zhu X, Zhu L, Li Y, Duan Z, Chen W, Alvarez P (2007) Developmental toxicity in zebrafish (Danio rerio) embryos after exposure to manufactured nanomaterials: buckminsterfullerene aggregates (nC60) and fullerol. Environ Toxicol Chem 26:976–979

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author (BBK) gratefully acknowledges the Department of Biotechnology (DBT) of the government of India for providing the Overseas Associate Fellowship for NE Region 2014 and Dibrugarh University, Dibrugarh, Assam, India, for permitting to undertake the proposed study at the University of South Florida, USA.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, 786004, India

    Bibhuti B. Kakoti & Manjir Sarma Kataki

  2. Department of Pharmaceutical Sciences, USF College of Pharmacy, University of South, Florida, Tampa, FL, 33612, USA

    Yashwant Pathak

Authors
  1. Bibhuti B. Kakoti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manjir Sarma Kataki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yashwant Pathak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yashwant Pathak .

Editor information

Editors and Affiliations

  1. College of Pharmacy, University of South Florida Health, Tampa, Florida, USA

    Yashwant Pathak

  2. College of Pharmacy, University of South Florida Health, Tampa, Florida, USA

    Vijaykumar Sutariya

  3. College of Pharmacy, University of South Florida, Tampa, Florida, USA

    Anjali A. Hirani

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Kakoti, B.B., Kataki, M.S., Pathak, Y. (2016). Nanotoxicity of Nanobiomaterials in Ocular System and Its Evaluation. In: Pathak, Y., Sutariya, V., Hirani, A. (eds) Nano-Biomaterials For Ophthalmic Drug Delivery. Springer, Cham. https://doi.org/10.1007/978-3-319-29346-2_22

Download citation

Publish with us

Policies and ethics

Search

Navigation