Skip to main content
SpringerLink
Log in

Nanotoxicology and Regulatory Affairs

  • Chapter
  • First Online:
Nanomedicine

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Like other parts of the nanotechnology revolution nanomedicines hold great promise and in the case of nanomedicines the potential for more efficient therapies. Engineered nanomaterials that are used as nanomedicines for therapeutic and diagnostic purposes are often designed to specifically interact with cells of tissues and organs of the human body. However, the unique physicochemical properties of particles at the nanoscale may contribute to adverse effects requiring nanomaterial-specific safety considerations. Therefore, before nanomedicines can be approved by organisations such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) and reach the market, safety, efficiency and efficacy have to be shown. Beginning with some short critical remarks, this chapter addresses the toxicology of nanomaterials referred to as nanotoxicology with special attention to nanomedical applications. The second part of this book chapter will briefly describe the general drug approval process, introduce risk assessment procedures and give an overview of safety and regulatory challenges for nanomedicines.

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. Project on Emerging Nanotechnologies. (2014). http://www.nanotechproject.org/

  2. Chan VS (2006) Nanomedicine: an unresolved regulatory issue. Regul Toxicol Pharmacol 46:218–224

    Article  PubMed  CAS  Google Scholar 

  3. Donaldson K, Stone V (2003) Current hypotheses on the mechanisms of toxicity of ultrafine particles. Ann Ist Super Sanita 39:405–410

    PubMed  CAS  Google Scholar 

  4. Schwarze PE, Ovrevik J, Lag M, Refsnes M, Nafstad P, Hetland RB et al (2006) Particulate matter properties and health effects: consistency of epidemiological and toxicological studies. Hum Exp Toxicol 25:559–579

    Article  PubMed  CAS  Google Scholar 

  5. Donaldson K, Stone V, Tran CL, Kreyling W, Borm PJ (2004) Nanotoxicology. Occup Environ Med 61:727–728

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Maynard AD, Warheit DB, Philbert MA (2011) The new toxicology of sophisticated materials: nanotoxicology and beyond. Toxicol Sci 120(Suppl 1):S109–S129

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M (2014) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 8:233–278

    Article  PubMed  CAS  Google Scholar 

  8. Stone V, Nowack B, Baun A, van den Brink N, Kammer F, Dusinska M et al (2010) Nanomaterials for environmental studies: classification, reference material issues, and strategies for physico-chemical characterisation. Sci Total Environ 408:1745–1754

    Article  PubMed  CAS  Google Scholar 

  9. Karlsson HL (2010) The comet assay in nanotoxicology research. Anal Bioanal Chem 398:651–666

    Article  PubMed  CAS  Google Scholar 

  10. 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  PubMed  CAS  Google Scholar 

  11. Landsiedel R, Kapp MD, Schulz M, Wiench K, Oesch F (2009) Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations—many questions, some answers. Mutat Res 681:241–258

    Article  PubMed  CAS  Google Scholar 

  12. Monteiro-Riviere NA, Inman AO, Zhang LW (2009) Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. Toxicol Appl Pharmacol 234:222–235

    Article  PubMed  CAS  Google Scholar 

  13. Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Landsiedel R, Ma-Hock L, Kroll A, Hahn D, Schnekenburger J, Wiench K et al (2010) Testing metal-oxide nanomaterials for human safety. Adv Mater 22:2601–2627

    Article  PubMed  CAS  Google Scholar 

  15. Kumar S, Verma MK, Srivastava AK (2013) Ultrafine particles in urban ambient air and their health perspectives. Rev Environ Health 28:117–128

    Article  PubMed  CAS  Google Scholar 

  16. Society of Toxicology SOT (2005). http://www.toxicology.org/ai/pub/si05/SI05_Define.asp. Ref Type: Online Source

  17. Oberdorster G (2010) Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J Intern Med 267:89–105

    Article  PubMed  CAS  Google Scholar 

  18. Zhu M, Nie G, Meng H, Xia T, Nel A, Zhao Y (2013) Physicochemical properties determine nanomaterial cellular uptake, transport, and fate. Acc Chem Res 46:622–631

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Zhu M, Perrett S, Nie G (2013) Understanding the particokinetics of engineered nanomaterials for safe and effective therapeutic applications. Small 9:1619–1634

    Article  PubMed  CAS  Google Scholar 

  20. Foss Hansen S, Larsen BH, Olsen SI, Baun A (2007) Categorization framework to aid hazard identification of nanomaterials. Nanotoxicology 1:243–250

    Article  CAS  Google Scholar 

  21. Baeza-Squiban A, Boland S, Hussain S, Marano F (2009) Health effects of nanoparticles. In: General, applied and systems toxicology. John Wiley & Sons, Ltd, Chichester

    Google Scholar 

  22. Borm PJ, Kreyling W (2004) Toxicological hazards of inhaled nanoparticles—potential implications for drug delivery. J Nanosci Nanotechnol 4:521–531

    Article  PubMed  CAS  Google Scholar 

  23. Gellein K, Syversen T (2009) Nanotoxicology—the toxicology of nanomaterials. In: General, applied and systems toxicology. John Wiley & Sons, Ltd, Chichester

    Google Scholar 

  24. Cho M, Cho WS, Choi M, Kim SJ, Han BS, Kim SH et al (2009) The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles. Toxicol Lett 189:177–183

    Article  PubMed  CAS  Google Scholar 

  25. Hussain S, Boland S, Baeza-Squiban A, Hamel R, Thomassen LC, Martens JA et al (2009) Oxidative stress and proinflammatory effects of carbon black and titanium dioxide nanoparticles: role of particle surface area and internalized amount. Toxicology 260:142–149

    Article  PubMed  CAS  Google Scholar 

  26. Stoeger T, Reinhard C, Takenaka S, Schroeppel A, Karg E, Ritter B et al (2006) Instillation of six different ultrafine carbon particles indicates a surface area threshold dose for acute lung inflammation in mice. Environ Health Perspect 114:328–333

    Article  PubMed  PubMed Central  Google Scholar 

  27. Piret JP, Vankoningsloo S, Mejia J, Noel F, Boilan E, Lambinon F et al (2012) Differential toxicity of copper (II) oxide nanoparticles of similar hydrodynamic diameter on human differentiated intestinal Caco-2 cell monolayers is correlated in part to copper release and shape. Nanotoxicology 6:789–803

    Article  PubMed  CAS  Google Scholar 

  28. Tarantola M, Pietuch A, Schneider D, Rother J, Sunnick E, Rosman C et al (2011) Toxicity of gold-nanoparticles: synergistic effects of shape and surface functionalization on micromotility of epithelial cells. Nanotoxicology 5:254–268

    Article  PubMed  CAS  Google Scholar 

  29. World Health Organization (1997) Determination of airborne fibre number concentrations: a recommended method, by phase-contrast optical microscopy, membrane filter method. World Health Organization, Geneva

    Google Scholar 

  30. Feng W, Nie W, He C, Zhou X, Chen L, Qiu K et al (2014) Effect of pH-responsive alginate/chitosan multilayers coating on delivery efficiency, cellular uptake and biodistribution of mesoporous silica nanoparticles based nanocarriers. ACS Appl Mater Interfaces 6:8447–8460

    Article  PubMed  CAS  Google Scholar 

  31. Ogawara K, Furumoto K, Nagayama S, Minato K, Higaki K, Kai T et al (2004) Pre-coating with serum albumin reduces receptor-mediated hepatic disposition of polystyrene nanosphere: implications for rational design of nanoparticles. J Control Release 100:451–455

    Article  PubMed  CAS  Google Scholar 

  32. Cedervall T, Lynch I, Lindman S, Berggard T, Thulin E, Nilsson H et al (2007) Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc Natl Acad Sci U S A 104:2050–2055

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Deng ZJ, Mortimer G, Schiller T, Musumeci A, Martin D, Minchin RF (2009) Differential plasma protein binding to metal oxide nanoparticles. Nanotechnology 20:455101

    Article  PubMed  CAS  Google Scholar 

  34. Vertegel AA, Siegel RW, Dordick JS (2004) Silica nanoparticle size influences the structure and enzymatic activity of adsorbed lysozyme. Langmuir 20:6800–6807

    Article  PubMed  Google Scholar 

  35. Casals E, Puntes VF (2012) Inorganic nanoparticle biomolecular corona: formation, evolution and biological impact. Nanomedicine (Lond) 7:1917–1930

    Article  CAS  Google Scholar 

  36. Frohlich E (2012) The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine 7:5577–5591

    Article  PubMed  PubMed Central  Google Scholar 

  37. Magrez A, Kasas S, Salicio V, Pasquier N, Seo JW, Celio M et al (2006) Cellular toxicity of carbon-based nanomaterials. Nano Lett 6:1121–1125

    Article  PubMed  CAS  Google Scholar 

  38. Yang SH, Heo D, Park J, Na S, Suh JS, Haam S et al (2012) Role of surface charge in cytotoxicity of charged manganese ferrite nanoparticles towards macrophages. Nanotechnology 23:505702

    Article  PubMed  CAS  Google Scholar 

  39. Bhattacharjee S, Ershov D, Gucht J, Alink GM, Rietjens IM, Zuilhof H et al (2013) Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles. Nanotoxicology 7:71–84

    Article  PubMed  CAS  Google Scholar 

  40. Asati A, Santra S, Kaittanis C, Perez JM (2010) Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano 4:5321–5331

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Bhattacharjee S, de Haan LH, Evers NM, Jiang X, Marcelis AT, Zuilhof H et al (2010) Role of surface charge and oxidative stress in cytotoxicity of organic monolayer-coated silicon nanoparticles towards macrophage NR8383 cells. Part Fibre Toxicol 7:25

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Xu M, Zhao Y, Feng M (2012) Polyaspartamide derivative nanoparticles with tunable surface charge achieve highly efficient cellular uptake and low cytotoxicity. Langmuir 28:11310–11318

    Article  PubMed  CAS  Google Scholar 

  43. Sayes CM, Liang F, Hudson JL, Mendez J, Guo W, Beach JM et al (2006) Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett 161:135–142

    Article  PubMed  CAS  Google Scholar 

  44. Chiu CC, Moore PB, Shinoda W, Nielsen SO (2009) Size-dependent hydrophobic to hydrophilic transition for nanoparticles: a molecular dynamics study. J Chem Phys 131:244706

    Article  PubMed  CAS  Google Scholar 

  45. Ogris M, Brunner S, Schuller S, Kircheis R, Wagner E (1999) PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther 6:595–605

    Article  PubMed  CAS  Google Scholar 

  46. Zhao J, Castranova V (2011) Toxicology of nanomaterials used in nanomedicine. J Toxicol Environ Health B Crit Rev 14:593–632

    Article  PubMed  CAS  Google Scholar 

  47. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W et al (2004) Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16:437–445

    Article  PubMed  CAS  Google Scholar 

  48. Hagens WI, Oomen AG, De Jong WH, Cassee FR, Sips AJ (2007) What do we (need to) know about the kinetic properties of nanoparticles in the body? Regul Toxicol Pharmacol 49:217–229

    Article  PubMed  CAS  Google Scholar 

  49. Volkheimer G (1974) Passage of particles through the wall of the gastrointestinal tract. Environ Health Perspect 9:215–225

    PubMed  PubMed Central  CAS  Google Scholar 

  50. Volkheimer G, Schulz FH, Aurich I, Strauch S, Beuthin K, Wendlandt H (1968) Persorption of particles. Digestion 1:78–80

    Article  PubMed  CAS  Google Scholar 

  51. Volkheimer G, Schulz FH (1968) The phenomenon of persorption. Digestion 1:213–218

    Article  PubMed  CAS  Google Scholar 

  52. De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ, Geertsma RE (2008) Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29:1912–1919

    Article  PubMed  CAS  Google Scholar 

  53. Zhu MT, Feng WY, Wang Y, Wang B, Wang M, Ouyang H et al (2009) Particokinetics and extrapulmonary translocation of intratracheally instilled ferric oxide nanoparticles in rats and the potential health risk assessment. Toxicol Sci 107:342–351

    Article  PubMed  CAS  Google Scholar 

  54. Chen J, Tan M, Nemmar A, Song W, Dong M, Zhang G et al (2006) Quantification of extrapulmonary translocation of intratracheal-instilled particles in vivo in rats: effect of lipopolysaccharide. Toxicology 222:195–201

    Article  PubMed  CAS  Google Scholar 

  55. Meiring JJ, Borm PJ, Bagate K, Semmler M, Seitz J, Takenaka S et al (2005) The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung. Part Fibre Toxicol 2:3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902

    Article  PubMed  CAS  Google Scholar 

  57. Gould GW, Lippincott-Schwartz J (2009) New roles for endosomes: from vesicular carriers to multi-purpose platforms. Nat Rev Mol Cell Biol 10:287–292

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Harush-Frenkel O, Rozentur E, Benita S, Altschuler Y (2008) Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells. Biomacromolecules 9:435–443

    Article  PubMed  CAS  Google Scholar 

  59. Mayor S, Pagano RE (2007) Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol 8:603–612

    Article  PubMed  CAS  Google Scholar 

  60. Zhang LW, Monteiro-Riviere NA (2009) Mechanisms of quantum dot nanoparticle cellular uptake. Toxicol Sci 110:138–155

    Article  PubMed  CAS  Google Scholar 

  61. Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y (2011) Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 7:1322–1337

    Article  PubMed  CAS  Google Scholar 

  62. Mortimer M, Kasemets K, Kahru A (2010) Toxicity of ZnO and CuO nanoparticles to ciliated protozoa Tetrahymena thermophila. Toxicology 269:182–189

    Article  PubMed  CAS  Google Scholar 

  63. Beer C, Foldbjerg R, Hayashi Y, Sutherland DS, Autrup H (2012) Toxicity of silver nanoparticles—nanoparticle or silver ion? Toxicol Lett 208:286–292

    Article  PubMed  CAS  Google Scholar 

  64. Xia T, Kovochich M, Liong M, Madler L, Gilbert B, Shi H et al (2008) Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano 2:2121–2134

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Jiang X, Miclaus T, Wang L, Foldbjerg R, Sutherland DS, Autrup H et al (2014) Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity. Nanotoxicology 9:181–189

    Article  PubMed  CAS  Google Scholar 

  66. Borm P, Klaessig FC, Landry TD, Moudgil B, Pauluhn J, Thomas K et al (2006) Research strategies for safety evaluation of nanomaterials: Part V. Role of dissolution in biological fate and effects of nanoscale particles. Toxicol Sci 90:23–32

    Article  PubMed  CAS  Google Scholar 

  67. Ha ES, Choo GH, Baek IH, Kim JS, Cho W, Jung YS et al (2014) Dissolution and bioavailability of lercanidipine-hydroxypropylmethyl cellulose nanoparticles with surfactant. Int J Biol Macromol 72C:218–222

    Google Scholar 

  68. Martin MN, Allen AJ, MacCuspie RI, Hackley VA (2014) Dissolution, agglomerate morphology, and stability limits of protein-coated silver nanoparticles. Langmuir 30(38):11442–11452

    Article  PubMed  CAS  Google Scholar 

  69. Lanzl CA, Baltrusaitis J, Cwiertny DM (2012) Dissolution of hematite nanoparticle aggregates: influence of primary particle size, dissolution mechanism, and solution pH. Langmuir 28:15797–15808

    Article  PubMed  CAS  Google Scholar 

  70. Fraga S, Brandao A, Soares ME, Morais T, Duarte JA, Pereira L et al (2014) Short- and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration. Nanomedicine 10:1757–1766

    PubMed  CAS  Google Scholar 

  71. Ballantyne B, Marrs TC, Syversen T (2009) Basic elements of toxicology. In: General, applied and systems toxicology. John Wiley & Sons, Ltd, Chichester

    Google Scholar 

  72. Lison D, Carbonnelle P, Mollo L, Lauwerys R, Fubini B (1995) Physicochemical mechanism of the interaction between cobalt metal and carbide particles to generate toxic activated oxygen species. Chem Res Toxicol 8:600–606

    Article  PubMed  CAS  Google Scholar 

  73. Guo B, Zebda R, Drake SJ, Sayes CM (2009) Synergistic effect of co-exposure to carbon black and Fe2O3 nanoparticles on oxidative stress in cultured lung epithelial cells. Part Fibre Toxicol 6:4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Sayes CM, Banerjee N, Romoser AA (2009) The role of oxidative stress in nanotoxicology. In: General, applied and systems toxicology. John Wiley & Sons, Ltd, Chichester

    Google Scholar 

  75. Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG et al (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30:3891–3914

    Article  PubMed  CAS  Google Scholar 

  76. Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627

    Article  PubMed  CAS  Google Scholar 

  77. Winterbourn CC (2008) Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol 4:278–286

    Article  PubMed  CAS  Google Scholar 

  78. Cattley RC, Glover SE (1993) Elevated 8-hydroxydeoxyguanosine in hepatic DNA of rats following exposure to peroxisome proliferators: relationship to carcinogenesis and nuclear localization. Carcinogenesis 14:2495–2499

    Article  PubMed  CAS  Google Scholar 

  79. Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ et al (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharmacol 233:404–410

    Article  PubMed  CAS  Google Scholar 

  80. Foldbjerg R, Dang DA, Autrup H (2011) Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 85:743–750

    Article  PubMed  CAS  Google Scholar 

  81. Jiang X, Foldbjerg R, Miclaus T, Wang L, Singh R, Hayashi Y et al (2013) Multi-platform genotoxicity analysis of silver nanoparticles in the model cell line CHO-K1. Toxicol Lett 222:55–63

    Article  PubMed  CAS  Google Scholar 

  82. Kumar A, Dhawan A (2013) Genotoxic and carcinogenic potential of engineered nanoparticles: an update. Arch Toxicol 87:1883–1900

    Article  PubMed  CAS  Google Scholar 

  83. Ng CT, Li JJ, Bay BH, Yung LY (2010) Current studies into the genotoxic effects of nanomaterials. J Nucleic Acids 2010:947859

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Cheng Y, Dai Q, Morshed RA, Fan X, Wegscheid ML, Wainwright DA et al (2014) Blood-brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging. Small 10:5137–5150

    PubMed  PubMed Central  CAS  Google Scholar 

  85. Hwang SR, Kim K (2014) Nano-enabled delivery systems across the blood-brain barrier. Arch Pharm Res 37:24–30

    Article  PubMed  CAS  Google Scholar 

  86. Cupaioli FA, Zucca FA, Boraschi D, Zecca L (2014) Engineered nanoparticles. How brain friendly is this new guest? Prog Neurobiol 119–120C:20–38

    Article  CAS  Google Scholar 

  87. Sadauskas E, Wallin H, Stoltenberg M, Vogel U, Doering P, Larsen A et al (2007) Kupffer cells are central in the removal of nanoparticles from the organism. Part Fibre Toxicol 4:10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Huang JY, Lu YM, Wang H, Liu J, Liao MH, Hong LJ et al (2013) The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain. Biomaterials 34:7960–7970

    Article  PubMed  CAS  Google Scholar 

  89. Voigt N, Henrich-Noack P, Kockentiedt S, Hintz W, Tomas J, Sabel BA (2014) Surfactants, not size or zeta-potential influence blood-brain barrier passage of polymeric nanoparticles. Eur J Pharm Biopharm 87:19–29

    Article  PubMed  CAS  Google Scholar 

  90. Gibson RM (2007) Understanding the potential neurotoxicology of nanoparticles. In: Nanotoxicology: characterization, dosing, and health effects. Informa Healthcare, pp 99–316

    Google Scholar 

  91. Mistry A, Stolnik S, Illum L (2009) Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm 379:146–157

    Article  PubMed  CAS  Google Scholar 

  92. Mistry A, Glud SZ, Kjems J, Randel J, Howard KA, Stolnik S et al (2009) Effect of physicochemical properties on intranasal nanoparticle transit into murine olfactory epithelium. J Drug Target 17:543–552

    Article  PubMed  CAS  Google Scholar 

  93. Hopkins LE, Patchin ES, Chiu PL, Brandenberger C, Smiley-Jewell S, Pinkerton KE (2014) Nose-to-brain transport of aerosolised quantum dots following acute exposure. Nanotoxicology 8:885–893

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Aschner M, Erikson KM, Dorman DC (2005) Manganese dosimetry: species differences and implications for neurotoxicity. Crit Rev Toxicol 35:1–32

    Article  PubMed  CAS  Google Scholar 

  95. Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J et al (2006) Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ Health Perspect 114:1172–1178

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Ze Y, Sheng L, Zhao X, Hong J, Ze X, Yu X et al (2014) TiO2 nanoparticles induced hippocampal neuroinflammation in mice. PLoS One 9:e92230

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Li XB, Zheng H, Zhang ZR, Li M, Huang ZY, Schluesener HJ et al (2009) Glia activation induced by peripheral administration of aluminum oxide nanoparticles in rat brains. Nanomedicine 5:473–479

    PubMed  CAS  Google Scholar 

  98. Wang J, Liu Y, Jiao F, Lao F, Li W, Gu Y et al (2008) Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO(2) nanoparticles. Toxicology 254:82–90

    Article  PubMed  CAS  Google Scholar 

  99. Song Y, Li X, Du X (2009) Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur Respir J 34:559–567

    Article  PubMed  CAS  Google Scholar 

  100. Yang W, Peters JI, Williams RO III (2008) Inhaled nanoparticles—a current review. Int J Pharm 356:239–247

    Article  PubMed  CAS  Google Scholar 

  101. Geiser M, Kreyling WG (2010) Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol 7:2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Donaldson K, Tran L, Jimenez LA, Duffin R, Newby DE, Mills N et al (2005) Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2:10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Simeonova PP, Erdely A (2009) Engineered nanoparticle respiratory exposure and potential risks for cardiovascular toxicity: predictive tests and biomarkers. Inhal Toxicol 21(Suppl 1):68–73

    Article  PubMed  CAS  Google Scholar 

  104. Simeonova P, Erdely A, Li Z (2007) Carbon nanotube exposure and risk for cardiovascular effects. In: Nanotoxicology: characterization, dosing, and health effects. Informa Healthcare, pp 237–246

    Google Scholar 

  105. Kelly B (2010) Nanomedicines: regulatory challenges and risks ahead. Scrip Regulatory Affairs

    Google Scholar 

  106. Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J (2013) The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine 9:1–14

    PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Public Health, Aarhus University, Bartholins Allé 2, 8000, Aarhus C, Denmark

    Christiane Beer

Authors
  1. Christiane Beer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christiane Beer .

Editor information

Editors and Affiliations

  1. Department of Molecular Biology and Gen, Interdisciplinary Nanoscience Center (i, Aarhus, Denmark

    Kenneth A. Howard

  2. Department of Biomedicine, Biophysical I, Aarhus University, Aarhus, Denmark

    Thomas Vorup-Jensen

  3. Britannia Bldg, 2nd Fl, Rm 226, Tel-Aviv Univ, Dept Cell Research, Tel-Aviv, Israel

    Dan Peer

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Controlled Release Society

About this chapter

Cite this chapter

Beer, C. (2016). Nanotoxicology and Regulatory Affairs. In: Howard, K., Vorup-Jensen, T., Peer, D. (eds) Nanomedicine. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3634-2_12

Download citation

Publish with us

Policies and ethics

Search

Navigation