Skip to main content
SpringerLink
Log in

Evaluation of Lung Toxicity of Biodegradable Nanoparticles

  • Chapter
  • First Online:
Targeted Drug Delivery : Concepts and Design

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

Abstract

Biodegradable nanoparticles display high therapeutic potentialities for drug delivery to or through the lungs. However, their interactions with lung cells can be assimilated to the ones described for particulate matter or inorganic manufactured nanoparticles. This is the reason why we discuss in the following chapter, the behavior of nanoparticles towards the different parts of the respiratory tract and the different models and tests that can be carried out to investigate the potential damaging effects of nanoparticles. Taken all together, the different studies using various experimental approaches (in vitro, ex vivo, or in vivo) conclude on no or slight toxicity of nanoparticles intended 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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Abbreviations

7-AAD:

7-Aminoactinomycin D

BAL:

Bronchoalveolar lavages

BALF:

Bronchoalveolar lavage fluids

BALT:

Bronchial associated lymphoid tissue

CLSM:

Confocal laser scanning microscopy

DPI:

Dry powder inhaler

DPPC:

1,2-Dipalmitoyl-sn-glycero-3-phosphocholine

ELISA:

Enzyme linked immunosorbent assay

IL:

Interleukin

IPL:

Isolated perfused lung

LDH:

Lactate dehydrogenase

MDI:

Metered dose inhaler

PEG:

Polyethylene glycol

PLA:

Poly(lactic acid)

PLGA:

Poly(lactide-co-glycolide)

PMN:

Polymorphonuclear

PVA:

Polyvinyl alcohol

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SLN:

Solid lipid nanoparticles

SP:

Surfactant proteins

TEM:

Transmission electronic microscopy

TNF-α:

Tumor necrosis factor-α

References

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

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Mu L, Sprando R (2010) Application of nanotechnology in cosmetics. Pharm Res 27: 1746–1749

    CAS  PubMed  Google Scholar 

  3. Choi SJ, Oh JM, Choy JH (2009) Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells. J Inorg Biochem 103:463–471

    CAS  PubMed  Google Scholar 

  4. Lin W, Huang YW, Zhou XD, Ma Y (2006) In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicol Appl Pharmacol 217:252–259

    CAS  PubMed  Google Scholar 

  5. Bhattacharya K, Davoren M, Boertz J, Schins R, Hoffmann E, Dopp E (2009) Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part Fibre Toxicol 6:1–11

    Google Scholar 

  6. Wang JX, Chen CY, Liu Y, Jiao F, Li W, Lao F, Li YF, Li B, Ge CC, Zhou GQ, Gao YX, Zhao YL, Chai ZF (2008) Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett 183:72–80

    CAS  PubMed  Google Scholar 

  7. Bachand GD, Allen A, Bachand M, Achyuthan KE, Seagrave JC, Brozik SM (2012) Cytotoxicity and inflammation in human alveolar epithelial cells following exposure to occupational levels of gold and silver nanoparticles. J Nanopart Res 14

    Google Scholar 

  8. Patton JS, Fishburn CS, Weers JG (2004) The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc 1:338–344

    CAS  PubMed  Google Scholar 

  9. Patton JS (1996) Mechanisms of macromolecule absorption by the lungs. Adv Drug Deliv Rev 19:3–36

    CAS  Google Scholar 

  10. Sung JC, Pulliam BL, Edwards DA (2007) Nanoparticles for drug delivery to the lungs. Trends Biotechnol 25:563–570

    CAS  PubMed  Google Scholar 

  11. Tsapis N, Bennett D, Jackson B, Weitz DA, Edwards DA (2002) Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci U S A 99:12001–12005

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Mansour HM, Rhee YS, Wu X (2009) Nanomedicine in pulmonary delivery. Int J Nanomedicine 4:299–319

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Weibel ER, Gomez DM (1962) Architecture of the human lung: use of quantitative methods establishes fundamental relations between size and number of lung structures. Science 137: 577–585

    CAS  PubMed  Google Scholar 

  14. Shelly MP, Lloyd GM, Park GR (1988) A review of the mechanisms and methods of humidification of inspired gases. Intensive Care Med 14:1–9

    CAS  PubMed  Google Scholar 

  15. Tsuda T, Noguchi H, Takumi Y, Aochi O (1977) Optimum humidification of air administered to a tracheastomy in dogs: scanning electron microscopy and surfactant studies. Br J Anaesth 49:965–977

    CAS  PubMed  Google Scholar 

  16. Patton JS, Byron PR (2007) Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6:67–74

    CAS  PubMed  Google Scholar 

  17. Rubin BK (2002) Physiology of airway mucus clearance. Respir Care 47:761–768

    PubMed  Google Scholar 

  18. Matsui H, Randell SH, Peretti SW, Davis CW, Boucher RC (1998) Coordinated clearance of periciliary liquid and mucus from airway surfaces. J Clin Invest 102:1125–1131

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Schuster BS, Suk JS, Woodworth GF, Hanes J (2013) Nanoparticle diffusion in respiratory mucus from humans without lung disease. Biomaterials 34:3439–3446

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Groneberg DA, Eynott PR, Lim S, Oates T, Wu R, Carlstedt I, Roberts P, Mccann B, Nicholson AG, Harrison BD, Chung KF (2002) Expression of respiratory mucins in fatal status asthmaticus and mild asthma. Histopathology 40:367–373

    CAS  PubMed  Google Scholar 

  21. Crapo JD, Barry BE, Gehr P, Bachofen M, Weibel ER (1982) Cell number and cell characteristics of the normal human lung. Am Rev Respir Dis 126:332–337

    CAS  PubMed  Google Scholar 

  22. Sherman MP, Ganz T (1992) Host defense in pulmonary alveoli. Annu Rev Physiol 54: 331–350

    CAS  PubMed  Google Scholar 

  23. Wright JR (1997) Immunomodulatory functions of surfactant. Physiol Rev 77:931–962

    CAS  PubMed  Google Scholar 

  24. Wright JR (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5:58–68

    CAS  PubMed  Google Scholar 

  25. Ruge CA, Kirch J, Cañadas O, Schneider M, Perez-Gil J, Schaefer UF, Casals C, Lehr C-M (2011) Uptake of nanoparticles by alveolar macrophages is triggered by surfactant protein A. Nanomedicine 7:690–693

    CAS  PubMed  Google Scholar 

  26. Randall TD (2010) Chapter 7 – bronchus-associated lymphoid tissue (BALT): structure and function. In: Sidonia F, Andrea C (eds) Advances in immunology. Academic, New York

    Google Scholar 

  27. Samet JM, Cheng PW (1994) The role of airway mucus in pulmonary toxicology. Environ Health Perspect 102(Suppl 2):89–103

    PubMed Central  PubMed  Google Scholar 

  28. Sahay G, Alakhova DY, Kabanov AV (2010) Endocytosis of nanomedicines. J Control Release 145:182–195

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Labiris NR, Dolovich MB (2003) Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 56:588–599

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Yang W, Peters JI, Williams RO 3rd (2008) Inhaled nanoparticles – a current review. Int J Pharm 356:239–247

    CAS  PubMed  Google Scholar 

  31. Suarez S, Hickey AJ (2000) Drug properties affecting aerosol behavior. Respir Care 45:652–666

    CAS  PubMed  Google Scholar 

  32. Sakagami M (2006) In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery. Adv Drug Deliv Rev 58: 1030–1060

    CAS  PubMed  Google Scholar 

  33. Byron PR (1986) Prediction of drug residence times in regions of the human respiratory-tract following aerosol inhalation. J Pharm Sci 75:433–438

    CAS  PubMed  Google Scholar 

  34. Heyder J, Rudolf G (1984) Mathematical-models of particle deposition in the human respiratory-tract. J Aerosol Sci 15:697–707

    Google Scholar 

  35. Heyder J, Gebhart J, Rudolf G, Schiller CF, Stahlhofen W (1986) Deposition of particles in the human respiratory-tract in the size range 0.005–15 μm. J Aerosol Sci 17:811–825

    Google Scholar 

  36. Beck-Broichsitter M, Merkel OM, Kissel T (2012) Controlled pulmonary drug and gene delivery using polymeric nano-carriers. J Control Release 161:214–224

    CAS  PubMed  Google Scholar 

  37. Li P, Liu DH, Sun XL, Liu CX, Liu YJ, Zhang N (2011) A novel cationic liposome formulation for efficient gene delivery via a pulmonary route. Nanotechnology 22

    Google Scholar 

  38. Weers J, Metzheiser B, Taylor G, Warren S, Meers P, Perkins WR (2009) A gamma scintigraphy study to investigate lung deposition and clearance of inhaled amikacin-loaded liposomes in healthy male volunteers. J Aerosol Med Pulm Drug Deliv 22:131–138

    CAS  PubMed  Google Scholar 

  39. Bruinenberg P, Serisier D, Cipolla D, Blanchard J (2010) Safety, tolerability and pharmacokinetics of novel liposomal ciprofloxacin formulations for inhalation in healthy volunteers and non-cystic bronchiectasis patients. B49. Bronchiectasis: cystic fibrosis and beyond. Meeting abstracts A3192–A3192

    Google Scholar 

  40. Schwarz C, Mehnert W, Lucks JS, Müller RH (1994) Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. J Control Release 30:83–96

    CAS  Google Scholar 

  41. Liu J, Gong T, Fu H, Wang C, Wang X, Chen Q, Zhang Q, He Q, Zhang Z (2008) Solid lipid nanoparticles for pulmonary delivery of insulin. Int J Pharm 356:333–344

    CAS  PubMed  Google Scholar 

  42. Ungaro F, D'angelo I, Coletta C, D'emmanuele Di Villa Bianca R, Sorrentino R, Perfetto B, Tufano MA, Miro A, La Rotonda MI, Quaglia F (2012) Dry powders based on plga nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers. J Control Release 157:149–159

    CAS  PubMed  Google Scholar 

  43. Huang M, Ma Z, Khor E, Lim L-Y (2002) Uptake of FITC-chitosan nanoparticles by A549 cells. Pharm Res 19:1488–1494

    CAS  PubMed  Google Scholar 

  44. Yang SG, Chang JE, Shin B, Park S, Na K, Shim CK (2010) (99)mTc-hematoporphyrin linked albumin nanoparticles for lung cancer targeted photodynamic therapy and imaging. J Mater Chem 20:9042–9046

    CAS  Google Scholar 

  45. Sahoo SK, Panyam J, Prabha S, Labhasetwar V (2002) Residual polyvinyl alcohol associated with poly (d, l-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J Control Release 82:105–114

    CAS  PubMed  Google Scholar 

  46. Bivas-Benita M, Van Meijgaarden KE, Franken KL, Junginger HE, Borchard G, Ottenhoff TH, Geluk A (2004) Pulmonary delivery of chitosan-DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis. Vaccine 22:1609–1615

    CAS  PubMed  Google Scholar 

  47. Zaru M, Mourtas S, Klepetsanis P, Fadda AM, Antimisiaris SG (2007) Liposomes for drug delivery to the lungs by nebulization. Eur J Pharm Biopharm 67:655–666

    CAS  PubMed  Google Scholar 

  48. Schwab JA, Zenkel M (1998) Filtration of particulates in the human nose. Laryngoscope 108:120–124

    CAS  PubMed  Google Scholar 

  49. Nowacki C, Heights A, Brisson AG (1985) Meterd dose inhaler. USA patent application 574,340

    Google Scholar 

  50. Sharma K, Somavarapu S, Colombani A, Govind N, Taylor KM (2012) Crosslinked chitosan nanoparticle formulations for delivery from pressurized metered dose inhalers. Eur J Pharm Biopharm 81:74–81

    CAS  PubMed  Google Scholar 

  51. Bivas-Benita M, Zwier R, Junginger HE, Borchard G (2005) Non-invasive pulmonary aerosol delivery in mice by the endotracheal route. Eur J Pharm Biopharm 61:214–218

    CAS  PubMed  Google Scholar 

  52. Newhouse MT (1992) Powder inhaler. USA patent application 484,069

    Google Scholar 

  53. Ohashi K, Kabasawa T, Ozeki T, Okada H (2009) One-step preparation of rifampicin/poly(lactic-co-glycolic acid) nanoparticle-containing mannitol microspheres using a four-fluid nozzle spray drier for inhalation therapy of tuberculosis. J Control Release 135:19–24

    CAS  PubMed  Google Scholar 

  54. Anton N, Jakhmola A, Vandamme TF (2012) Trojan microparticles for drug delivery. Pharmaceutics 4:1–25

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Grenha A, Seijo B, Remuñán-López C (2005) Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 25:427–437

    CAS  PubMed  Google Scholar 

  56. Tomoda K, Ohkoshi T, Nakajima T, Makino K (2008) Preparation and properties of inhalable nanocomposite particles: effects of the size, weight ratio of the primary nanoparticles in nanocomposite particles and temperature at a spray-dryer inlet upon properties of nanocomposite particles. Colloids Surf B Biointerfaces 64:70–76

    CAS  PubMed  Google Scholar 

  57. Tomoda K, Ohkoshi T, Hirota K, Sonavane GS, Nakajima T, Terada H, Komuro M, Kitazato K, Makino K (2009) Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer. Colloids Surf B Biointerfaces 71:177–182

    CAS  PubMed  Google Scholar 

  58. Gómez-Gaete C, Fattal E, Silva L, Besnard M, Tsapis N (2008) Dexamethasone acetate encapsulation into Trojan particles. J Control Release 128:41–49

    PubMed  Google Scholar 

  59. Zeng X-M, Macritchie HB, Marriott C, Martin GP (2007) Humidity-induced changes of the aerodynamic properties of dry powder aerosol formulations containing different carriers. Int J Pharm 333:45–55

    CAS  PubMed  Google Scholar 

  60. Shi L, Plumley CJ, Berkland C (2007) Biodegradable nanoparticle flocculates for dry powder aerosol formulation. Langmuir 23:10897–10901

    CAS  PubMed  Google Scholar 

  61. Ely L, Roa W, Finlay WH, Löbenberg R (2007) Effervescent dry powder for respiratory drug delivery. Eur J Pharm Biopharm 65:346–353

    CAS  PubMed  Google Scholar 

  62. Al-Hallak MHDK, Sarfraz MK, Azarmi S, Roa WH, Finlay WH, Rouleau C, Löbenberg R (2012) Distribution of effervescent inhalable nanoparticles after pulmonary delivery: an in vivo study. Ther Deliv 3:725–734

    CAS  PubMed  Google Scholar 

  63. Kim I, Byeon HJ, Kim TH, Lee ES, Oh KT, Shin BS, Lee KC, Youn YS (2012) Doxorubicin-loaded highly porous large PLGA microparticles as a sustained-release inhalation system for the treatment of metastatic lung cancer. Biomaterials 33:5574–5583

    CAS  PubMed  Google Scholar 

  64. Yang Y, Bajaj N, Xu P, Ohn K, Tsifansky MD, Yeo Y (2009) Development of highly porous large PLGA microparticles for pulmonary drug delivery. Biomaterials 30:1947–1953

    CAS  PubMed  Google Scholar 

  65. Hein S, Bur M, Schaefer UF, Lehr C-M (2011) A new pharmaceutical aerosol deposition device on cell cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations. Eur J Pharm Biopharm 77:132–138

    CAS  PubMed  Google Scholar 

  66. Cooney DJ, Hickey AJ (2011) Cellular response to the deposition of diesel exhaust particle aerosols onto human lung cells grown at the air–liquid interface by inertial impaction. Toxicol In Vitro 25:1953–1965

    CAS  PubMed  Google Scholar 

  67. Ungaro F, Giovino C, Coletta C, Sorrentino R, Miro A, Quaglia F (2010) Engineering gas-foamed large porous particles for efficient local delivery of macromolecules to the lung. Eur J Pharm Sci 41:60–70

    CAS  PubMed  Google Scholar 

  68. Tseng C-L, Wu SY-H, Wang W-H, Peng C-L, Lin F-H, Lin C-C, Young T-H, Shieh M-J (2008) Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer. Biomaterials 29:3014–3022

    CAS  PubMed  Google Scholar 

  69. Varshosaz J, Ghaffari S, Mirshojaei SF, Jafarian A, Atyabi F, Kobarfard F, Azarmi S (2013) Biodistribution of amikacin solid lipid nanoparticles after pulmonary delivery. BioMed Res Int 2013:8

    Google Scholar 

  70. Muhlfeld C, Gehr P, Rothen-Rutishauser B (2008) Translocation and cellular entering mechanisms of nanoparticles in the respiratory tract. Swiss Med Wkly 138:387–391

    PubMed  Google Scholar 

  71. Kunzli N, Tager IB (2005) Air pollution: from lung to heart. Swiss Med Wkly 135:697–702

    CAS  PubMed  Google Scholar 

  72. Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A (2010) Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 28:1300–1303

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Hillaireau H, Couvreur P (2009) Nanocarriers' entry into the cell: relevance to drug delivery. Cell Mol Life Sci 66:2873–2896

    CAS  PubMed  Google Scholar 

  74. Brzoska M, Langer K, Coester C, Loitsch S, Wagner TOF, Mallinckrodt CV (2004) Incorporation of biodegradable nanoparticles into human airway epithelium cells—in vitro study of the suitability as a vehicle for drug or gene delivery in pulmonary diseases. Biochem Biophys Res Commun 318:562–570

    CAS  PubMed  Google Scholar 

  75. Iversen T-G, Skotland T, Sandvig K (2011) Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies. Nano Today 6:176–185

    CAS  Google Scholar 

  76. Panyam J, Sahoo SK, Prabha S, Bargar T, Labhasetwar V (2003) Fluorescence and electron microscopy probes for cellular and tissue uptake of poly(d, l-lactide-co-glycolide) nanoparticles. Int J Pharm 262:1–11

    CAS  PubMed  Google Scholar 

  77. Mura S, Hillaireau H, Nicolas J, Le Droumaguet B, Gueutin C, Zanna S, Tsapis N, Fattal E (2011) Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells. Int J Nanomedicine 6:2591–2605

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Reul R, Tsapis N, Hillaireau H, Sancey L, Mura S, Recher M, Nicolas J, Coll J-L, Fattal E (2012) Near infrared labeling of PLGA for in vivo imaging of nanoparticles. Polym Chem 3:694–702

    CAS  Google Scholar 

  79. Cell Staining Simulation Tool Life Technologies (2013) Cell staining simulation tool [Online]. http://www.invitrogen.com/site/us/en/home/support/Research-Tools/Cell-Staining-Tool.html?CID=fl-cellstaintool. Accessed 11 Jul 2013

  80. CARTIERA MS, Johnson KM, Rajendran V, Caplan MJ, Saltzman WM (2009) The uptake and intracellular fate of PLGA nanoparticles in epithelial cells. Biomaterials 30:2790–2798

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Yang R, Yang S-G, Shim W-S, Cui F, Cheng G, Kim I-W, Kim D-D, Chung S-J, Shim C-K (2009) Lung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via transient formation of microaggregates. J Pharm Sci 98:970–984

    CAS  PubMed  Google Scholar 

  82. Semmler-Behnke M, Takenaka S, Fertsch S, Wenk A, Seitz J, Mayer P, Oberdorster G, Kreyling WG (2007) Efficient elimination of inhaled nanoparticles from the alveolar region: evidence for interstitial uptake and subsequent reentrainment onto airways epithelium. Environ Health Perspect 115:728–733

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Semmler M, Seitz J, Erbe F, Mayer P, Heyder J, Oberdorster G, Kreyling WG (2004) Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal Toxicol 16:453–459

    CAS  PubMed  Google Scholar 

  84. Tennant JR (1964) Evaluation of the trypan blue technique for determination of cell viability. Transplantation 2:685–694

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  86. Dailey LA, Jekel N, Fink L, Gessler T, Schmehl T, Wittmar M, Kissel T, Seeger W (2006) Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung. Toxicol Appl Pharmacol 215:100–108

    CAS  PubMed  Google Scholar 

  87. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148:2207–2216

    CAS  PubMed  Google Scholar 

  89. Jänicke RU, Sprengart ML, Wati MR, Porter AG (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273: 9357–9360

    PubMed  Google Scholar 

  90. Koopman G, Reutelingsperger CPM, Kuijten GAM, Keehnen RMJ, Pals ST, Vanoers MHJ (1994) Annexin-V for flow cytometric detection of phosphatidylserine expression on B-cells undergoing apoptosis. Blood 84:1415–1420

    CAS  PubMed  Google Scholar 

  91. Vanengeland M, Ramaekers FCS, Schutte B, Reutelingsperger CPM (1996) A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry 24:131–139

    CAS  Google Scholar 

  92. Singh NP, Mccoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    CAS  PubMed  Google Scholar 

  93. Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221

    CAS  PubMed  Google Scholar 

  94. Shoemaker RH, Wolpert-Defilippes MK, Kern DH, Lieber MM, Makuch RW, Melnick NR, Miller WT, Salmon SE, Simon RM, Venditti JM, von Hoff DD (1985) Application of a human tumor colony-forming assay to new drug screening. Cancer Res 45:2145–2153

    CAS  PubMed  Google Scholar 

  95. Jantzen K, Roursgaard M, Desler C, Loft S, Rasmussen LJ, Møller P (2012) Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. Mutagenesis 27:693–701

    CAS  PubMed  Google Scholar 

  96. Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82:291–295

    CAS  PubMed  Google Scholar 

  97. Sorg O (2004) Oxidative stress: a theoretical model or a biological reality? C R Biol 327:649–662

    CAS  PubMed  Google Scholar 

  98. Li N, Xia T, Nel AE (2008) The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 44:1689–1699

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Macnee W (2001) Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 429:195–207

    CAS  PubMed  Google Scholar 

  100. Repine JE, Bast A, Lankhorst IDA (1997) Oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 156:341–357

    CAS  PubMed  Google Scholar 

  101. Babior BM (2000) Phagocytes and oxidative stress. Am J Med 109:33–44

    CAS  PubMed  Google Scholar 

  102. Tsukagoshi H, Shimizu Y, Iwamae S, Hisada T, Ishizuka T, Iizuka K, Dobashi K, Mori M (2000) Evidence of oxidative stress in asthma and COPD: potential inhibitory effect of theophylline. Respir Med 94:584–588

    CAS  PubMed  Google Scholar 

  103. Lebel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231

    CAS  PubMed  Google Scholar 

  104. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126: 131–138

    CAS  PubMed  Google Scholar 

  105. Hensley K, Mou S, Pye Q (2003) Nitrite determination by colorimetric and fluorometric griess diazotization assays. In: Hensley K, Floyd R (eds) Methods in biological oxidative stress. Humana, New York

    Google Scholar 

  106. Nussler AK, Glanemann M, Schirmeier A, Liu L, Nussler NC (2006) Fluorometric measurement of nitrite/nitrate by 2,3-diaminonaphthalene. Nat Protoc 1:2223–2226

    CAS  PubMed  Google Scholar 

  107. Mccord JM, Fridovich I (1969) Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  108. Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem 44:276–287

    CAS  PubMed  Google Scholar 

  109. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    CAS  PubMed  Google Scholar 

  110. Rahman I, Kode A, Biswas SK (2007) Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 1:3159–3165

    Google Scholar 

  111. Kelley J (1990) Cytokines of the lung. Am Rev Respir Dis 141:765–788

    CAS  PubMed  Google Scholar 

  112. Galley HF, Webster NR (1996) The immuno-inflammatory cascade. Br J Anaesth 77:11–16

    CAS  PubMed  Google Scholar 

  113. Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 29:313–326

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Cromwell O, Hamid Q, Corrigan CJ, Barkans J, Meng Q, Collins PD, Kay AB (1992) Expression and generation of interleukin-8, IL-6 and granulocyte-macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1 beta and tumour necrosis factor-alpha. Immunology 77:330–337

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Sallusto F, Mackay CR, Lanzavecchia A (2000) The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol 18:593–620

    CAS  PubMed  Google Scholar 

  116. Polito AJ, Proud D (1998) Epithelial cells as regulators of airway inflammation. J Allergy Clin Immunol 102:714–718

    CAS  PubMed  Google Scholar 

  117. Dupont NC, Wang K, Wadhwa PD, Culhane JF, Nelson EL (2005) Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants. J Reprod Immunol 66:175–191

    CAS  PubMed  Google Scholar 

  118. Morgan E, Varro R, Sepulveda H, Ember JA, Apgar J, Wilson J, Lowe L, Chen R, Shivraj L, Agadir A, Campos R, Ernst D, Gaur A (2004) Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. Clin Immunol 110:252–266

    CAS  PubMed  Google Scholar 

  119. Tarnok A, Hambsch J, Chen R, Varro R (2003) Cytometric bead array to measure six cytokines in twenty-five microliters of serum. Clin Chem 49:1000–1002

    CAS  PubMed  Google Scholar 

  120. Djoba Siawaya JF, Roberts T, Babb C, Black G, Golakai HJ, Stanley K, Bapela NB, Hoal E, Parida S, Van Helden P, Walzl G (2008) An evaluation of commercial fluorescent bead-based luminex cytokine assays. PLoS One 3:e2535

    PubMed Central  PubMed  Google Scholar 

  121. Robertson J, Caldwell JR, Castle JR, Waldman RH (1976) Evidence for the presence of components of the alternative (Properdin) pathway of complement activation in respiratory secretions. J Immunol 117:900–903

    CAS  PubMed  Google Scholar 

  122. Lin H, Carlson DM, St George JA, Plopper CG, Wu R (1989) An ELISA method for the quantitation of tracheal mucins from human and nonhuman primates. Am J Respir Cell Mol Biol 1:41–48

    CAS  PubMed  Google Scholar 

  123. Phillips JE, Case NR, Celly C, Chapman RW, Hey JA, Minnicozzi M (2006) An enzyme-linked immunosorbent assay (ELISA) for the determination of mucin levels in bronchoalveolar lavage fluid. J Pharmacol Toxicol Methods 53:160–167

    CAS  PubMed  Google Scholar 

  124. Spurr-Michaud S, Argüeso P, Gipson I (2007) Assay of mucins in human tear fluid. Exp Eye Res 84:939–950

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Yang Y, Tsifansky MD, Shin S, Lin Q, Yeo Y (2011) Mannitol-guided delivery of ciprofloxacin in artificial cystic fibrosis mucus model. Biotechnol Bioeng 108:1441–1449

    CAS  PubMed  Google Scholar 

  126. Mura S, Hillaireau H, Nicolas J, Kerdine-Romer S, Le Droumaguet B, Delomenie C, Nicolas V, Pallardy M, Tsapis N, Fattal E (2011) Biodegradable nanoparticles meet the bronchial airway barrier: how surface properties affect their interaction with mucus and epithelial cells. Biomacromolecules 12:4136–4143

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  128. Hoet PH, Bruske-Hohlfeld I, Salata OV (2004) Nanoparticles - known and unknown health risks. J Nanobiotechnol 2:12

    Google Scholar 

  129. Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH (2009) Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 69: 8784–8789

    CAS  PubMed  Google Scholar 

  130. Park E-J, Yoon J, Choi K, Yi J, Park K (2009) Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. Toxicology 260: 37–46

    CAS  PubMed  Google Scholar 

  131. Shi Y, Wang F, He J, Yadav S, Wang H (2010) Titanium dioxide nanoparticles cause apoptosis in BEAS-2B cells through the caspase 8/t-Bid-independent mitochondrial pathway. Toxicol Lett 196:21–27

    CAS  PubMed  Google Scholar 

  132. Simon-Deckers A, Gouget B, Mayne-L'HERMITE M, Herlin-Boime N, Reynaud C, Carriere M (2008) In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes. Toxicology 253:137–146

    CAS  PubMed  Google Scholar 

  133. Fisher GL, Placke ME (1987) In vitro models of lung toxicity. Toxicology 47:71–93

    CAS  PubMed  Google Scholar 

  134. Phelps RM, Johnson BE, Ihde DC, Gazdar AF, Carbone DP, Mcclintock PR, Linnoila RI, Matthews MJ, Bunn PA, Carney D, Minna JD, Mulshine JL (1996) Nci-navy medical oncology branch cell line data base. J Cell Biochem 63:32–91

    Google Scholar 

  135. Dombu C, Carpentier R, Betbeder D (2012) Influence of surface charge and inner composition of nanoparticles on intracellular delivery of proteins in airway epithelial cells. Biomaterials 33:9117–9126

    CAS  PubMed  Google Scholar 

  136. Bivas-Benita M, Romeijn S, Junginger HE, Borchard G (2004) PLGA-PEI nanoparticles for gene delivery to pulmonary epithelium. Eur J Pharm Biopharm 58:1–6

    CAS  PubMed  Google Scholar 

  137. Fogh J, Fogh JM, Orfeo T (1977) One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 59:221–226

    CAS  PubMed  Google Scholar 

  138. Foster KA, Avery ML, Yazdanian M, Audus KL (2000) Characterization of the Calu-3 cell line as a tool to screen pulmonary drug delivery. Int J Pharm 208:1–11

    CAS  PubMed  Google Scholar 

  139. Fiegel J, Ehrhardt C, Schaefer U, Lehr C-M, Hanes J (2003) Large porous particle impingement on lung epithelial cell monolayers—toward improved particle characterization in the lung. Pharm Res 20:788–796

    CAS  PubMed  Google Scholar 

  140. Mathias NR, Timoszyk J, Stetsko PI, Megill JR, Smith RL, Wall DA (2002) Permeability characteristics of Calu-3 human bronchial epithelial cells: in vitro - in vivo correlation to predict lung absorption in rats. J Drug Target 10:31–40

    CAS  Google Scholar 

  141. Reddel RR, Ke Y, Gerwin BI, Mcmenamin MG, Lechner JF, Su RT, Brash DE, Park JB, Rhim JS, Harris CC (1988) Transformation of human bronchial epithelial cells by infection with sv40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes. Cancer Res 48:1904–1909

    CAS  PubMed  Google Scholar 

  142. Steerenberg PA, Zonnenberg JA, Dormans JA, Joon PN, Wouters IM, Van Bree L, Scheepers PT, Van Loveren H (1998) Diesel exhaust particles induced release of interleukin 6 and 8 by (primed) human bronchial epithelial cells (BEAS 2B) in vitro. Exp Lung Res 24:85–100

    CAS  PubMed  Google Scholar 

  143. Eom H-J, Choi J (2009) Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicol In Vitro 23:1326–1332

    CAS  PubMed  Google Scholar 

  144. Park E-J, Yi J, Chung K-H, Ryu D-Y, Choi J, Park K (2008) Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol Lett 180: 222–229

    CAS  PubMed  Google Scholar 

  145. Lieber M, Smith B, Szakal A, Nelson-Rees W, Todaro G (1976) A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer 17:62–70

    CAS  PubMed  Google Scholar 

  146. Foster KA, Oster CG, Mayer MM, Avery ML, Audus KL (1998) Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism. Exp Cell Res 243:359–366

    CAS  PubMed  Google Scholar 

  147. Rothen-Rutishauser B, Clift MJD, Jud C, Fink A, Wick P (2012) Human epithelial cells in vitro – are they an advantageous tool to help understand the nanomaterial-biological barrier interaction? Eur Nanotoxicol Lett 4:1–20

    Google Scholar 

  148. Yuan H, Miao J, Du YZ, You J, Hu FQ, Zeng S (2008) Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. Int J Pharm 348:137–145

    CAS  PubMed  Google Scholar 

  149. Chono S, Tanino T, Seki T, Morimoto K (2006) Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes. J Drug Target 14:557–566

    CAS  PubMed  Google Scholar 

  150. Witherden IR, Vanden Bon EJ, Goldstraw P, Ratcliffe C, Pastorino U, Tetley TD (2004) Primary human alveolar type II epithelial cell chemokine release. Am J Respir Cell Mol Biol 30:500–509

    CAS  PubMed  Google Scholar 

  151. O'hare MJ, Bond J, Clarke C, Takeuchi Y, Atherton AJ, Berry C, Moody J, Silver ARJ, Davies DC, Alsop AE, Neville AM, Jat PS (2001) Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells. Proc Natl Acad Sci 98:646–651

    PubMed Central  PubMed  Google Scholar 

  152. Kemp SJ, Thorley AJ, Gorelik J, Seckl MJ, O'HARE MJ, Arcaro A, Korchev Y, Goldstraw P, Tetley TD (2008) Immortalization of human alveolar epithelial cells to investigate nanoparticle uptake. Am J Respir Cell Mol Biol 39:591–597

    CAS  PubMed Central  PubMed  Google Scholar 

  153. Pohl C, Hermanns MI, Uboldi C, Bock M, Fuchs S, Dei-Anang J, Mayer E, Kehe K, Kummer W, Kirkpatrick CJ (2009) Barrier functions and paracellular integrity in human cell culture models of the proximal respiratory unit. Eur J Pharm Biopharm 72:339–349

    CAS  PubMed  Google Scholar 

  154. Mattek_Corporation. EpiAirway™ [Online]. http://www.mattek.com/456-an-in-vitro-model-of-human-airway-epithelium-epiairway-for-in-vitro-metabolism-toxicity-screening-and-drug-delivery-applications. Accessed 29 Sept 2013

  155. Epthelix. MucilAir™ [Online]. http://www.epithelix.com/content/view/6/5/lang,en/. Accessed 29 Sept 2013

  156. Constant S, Huang S, Caulfuty M, Bonfante R, Monachino M, Frauenfelder R, Wiszniewski L (2011) 28 Day repeated dose toxicity test on an in vitro cell model. Toxicol Lett 205 (Suppl):S58

    Google Scholar 

  157. Constant S, Huang S, Caulfuty M, Bonfante R, Monachino M, Frauenfelder R, Wiszniewski L (2011) A simple method for testing the toxicity of nanomaterials on 3D air–liquid interface human airway epithelia (MucilAir™). Toxicol Lett 205(Suppl):S284

    Google Scholar 

  158. Hayden P, Kaluzhny Y, Kubilus J, Ayehunie S, Kandarova H, Klausner M (2011) Use of normal human 3-dimensional (NHu-3D) tissue models (EpiDerm, EpiAirway) for nanotoxicology applications. Alternative to experimental animals. MatTek Corporation, Montréal, QC

    Google Scholar 

  159. Bérubé K, Prytherch Z, Job C, Hughes T (2010) Human primary bronchial lung cell constructs: the new respiratory models. Toxicology 278:311–318

    PubMed  Google Scholar 

  160. Hermanns MI, Unger RE, Kehe K, Peters K, Kirkpatrick CJ (2004) Lung epithelial cell lines in coculture with human pulmonary microvascular endothelial cells: development of an alveolo-capillary barrier in vitro. Lab Invest 84:736–752

    CAS  PubMed  Google Scholar 

  161. Papritz M, Pohl C, Wübbeke C, Moisch M, Hofmann H, Hermanns MI, Thiermann H, Kirkpatrick CJ, Kehe K (2010) Side-specific effects by cadmium exposure: apical and basolateral treatment in a coculture model of the blood–air barrier. Toxicol Appl Pharmacol 245:361–369

    CAS  PubMed  Google Scholar 

  162. Wottrich R, Diabaté 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

    CAS  PubMed  Google Scholar 

  163. Abbas I, Saint-Georges F, Billet S, Verdin A, Mulliez P, Shirali P, Garçon G (2009) Air pollution particulate matter (PM2.5)-induced gene expression of volatile organic compound and/or polycyclic aromatic hydrocarbon-metabolizing enzymes in an in vitro coculture lung model. Toxicol In Vitro 23:37–46

    CAS  PubMed  Google Scholar 

  164. Wang S, Young RS, Sun NN, Witten ML (2002) In vitro cytokine release from rat type II pneumocytes and alveolar macrophages following exposure to JP-8 jet fuel in co-culture. Toxicology 173:211–219

    CAS  PubMed  Google Scholar 

  165. Stříž I, Slavčev A, Kalanin J, Jarešová M, Rennard SI (2001) Cell–cell contacts with epithelial cells modulate the phenotype of human macrophages. Inflammation 25:241–246

    PubMed  Google Scholar 

  166. Striz I, Wang YM, Teschler H, Sorg C, Costabel U (1993) Phenotypic markers of alveolar macrophage maturation in pulmonary sarcoidosis. Lung 171:293–303

    CAS  PubMed  Google Scholar 

  167. Rothen-Rutishauser BM, Kiama SG, Gehr P (2005) A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am J Respir Cell Mol Biol 32:281–289

    CAS  PubMed  Google Scholar 

  168. Müller L, Riediker M, Wick P, Mohr M, Gehr P, Rothen-Rutishauser B (2010) Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. J R Soc Interface 7:S27–S40

    PubMed Central  PubMed  Google Scholar 

  169. Alfaro-Moreno E, Nawrot TS, Vanaudenaerde BM, Hoylaerts MF, Vanoirbeek JA, Nemery B, Hoet PHM (2008) Co-cultures of multiple cell types mimic pulmonary cell communication in response to urban pm10. Eur Respir J 32:1184–1194

    CAS  PubMed  Google Scholar 

  170. Mehendale HM, Angevine LS, Ohmiya Y (1981) The isolated perfused lung—a critical evaluation. Toxicology 21:1–36

    CAS  PubMed  Google Scholar 

  171. Byron PR, Roberts NS, Clark AR (1986) An isolated perfused rat lung preparation for the study of aerosolized drug deposition and absorption. J Pharm Sci 75:168–171

    CAS  PubMed  Google Scholar 

  172. Meiring JJ, Borm PJ, Bagate K, Semmler M, Seitz J, Takenaka S, Kreyling WG (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

    PubMed Central  PubMed  Google Scholar 

  173. Beck-Broichsitter M, Gauss J, Packhaeuser CB, Lahnstein K, Schmehl T, Seeger W, Kissel T, Gessler T (2009) Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model. Int J Pharm 367:169–178

    CAS  PubMed  Google Scholar 

  174. Beck-Broichsitter M, Gauss J, Gessler T, Seeger W, Kissel T, Schmehl T (2010) Pulmonary targeting with biodegradable salbutamol-loaded nanoparticles. J Aerosol Med Pulm Drug Deliv 23:47–57

    CAS  PubMed  Google Scholar 

  175. Hamoir J, Nemmar A, Halloy D, Wirth D, Vincke G, Vanderplasschen A, Nemery B, Gustin P (2003) Effect of polystyrene particles on lung microvascular permeability in isolated perfused rabbit lungs: role of size and surface properties. Toxicol Appl Pharmacol 190: 278–285

    CAS  PubMed  Google Scholar 

  176. Nemmar A, Hamoir J, Nemery B, Gustin P (2005) Evaluation of particle translocation across the alveolo-capillary barrier in isolated perfused rabbit lung model. Toxicology 208: 105–113

    CAS  PubMed  Google Scholar 

  177. Beck-Broichsitter M, Schmehl T, Seeger W, Gessler T (2011) Evaluating the controlled release properties of inhaled nanoparticles using isolated, perfused, and ventilated lung models. J Nanomater 2011

    Google Scholar 

  178. Kirch J, Schneider A, Abou B, Hopf A, Schaefer UF, Schneider M, Schall C, Wagner C, Lehr C-M (2012) Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus. Proc Natl Acad Sci 109:18355–18360

    CAS  PubMed Central  PubMed  Google Scholar 

  179. Huang YY, Wang CH (2006) Pulmonary delivery of insulin by liposomal carriers. J Control Release 113:9–14

    CAS  PubMed  Google Scholar 

  180. Bi R, Shao W, Wang Q, Zhang N (2009) Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery. J Biomed Nanotechnol 5:84–92

    CAS  PubMed  Google Scholar 

  181. Pandey R, Khuller GK (2005) Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis. Tuberculosis (Edinb) 85:227–234

    CAS  Google Scholar 

  182. Yamamoto H, Kuno Y, Sugimoto S, Takeuchi H, Kawashima Y (2005) Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions. J Control Release 102:373–381

    CAS  PubMed  Google Scholar 

  183. Mcintire GL, Bacon ER, Toner JL, Cornacoff JB, Losco PE, Illig KJ, Nikula KJ, Muggenburg BA, Ketai L (1998) Pulmonary delivery of nanoparticles of insoluble, iodinated CT x-ray contrast agents to lung draining lymph nodes in dogs. J Pharm Sci 87:1466–1470

    CAS  PubMed  Google Scholar 

  184. Schreier H, Mcnicol KJ, Ausborn M, Soucy DM, Derendorf H, Stecenko AA, Gonzalezrothi RJ (1992) Pulmonary delivery of amikacin liposomes and acute liposome toxicity in the sheep. Int J Pharm 87:183–193

    CAS  Google Scholar 

  185. Nassimi M, Schleh C, Lauenstein H-D, Hussein R, Lübbers K, Pohlmann G, Switalla S, Sewald K, Müller M, Krug N, Müller-Goymann CC, Braun A (2009) Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models. Inhal Toxicol 21:104–109

    CAS  PubMed  Google Scholar 

  186. Grabowski N, Hillaireau H, Vergnaud J, Aragao LS, Kerdine-Romer S, Pallardy M, Tsapis N, Fattal E (2013) Toxicity of surface-modified PLGA nanoparticles toward lung alveolar epithelial cells. Int J Pharm 454(2):686–694

    CAS  PubMed  Google Scholar 

  187. Chuan J, Li Y, Yang L, Sun X, Zhang Q, Gong T, Zhang Z (2013) Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles. J Nanopart Res 15:1–9

    Google Scholar 

  188. Thomas C, Rawat A, Hope-Weeks L, Ahsan F (2010) Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine responses to hepatitis B vaccine. Mol Pharm 8:405–415

    Google Scholar 

  189. Howell M, Mallela J, Wang C, Ravi S, Dixit S, Garapati U, Mohapatra S (2013) Manganese-loaded lipid-micellar theranostics for simultaneous drug and gene delivery to lungs. J Control Release 167:210–218

    CAS  PubMed Central  PubMed  Google Scholar 

  190. Nassimi M, Schleh C, Lauenstein HD, Hussein R, Hoymann HG, Koch W, Pohlmann G, Krug N, Sewald K, Rittinghausen S, Braun A, Muller-Goymann C (2010) A toxicological evaluation of inhaled solid lipid nanoparticles used as a potential drug delivery system for the lung. Eur J Pharm Biopharm 75:107–116

    CAS  PubMed  Google Scholar 

  191. Hussain S, Vanoirbeek JAJ, Haenen S, Haufroid V, Boland S, Marano F, Nemery B, Hoet PHM (2013) Prior lung inflammation impacts on body distribution of gold nanoparticles. BioMed Res Int 2013:6

    Google Scholar 

  192. Verma NK, Crosbie-Staunton K, Satti A, Gallagher S, Ryan KB, Doody T, Mcatamney C, Macloughlin R, Galvin P, Burke CS, Volkov Y, Gun’ko YK (2013) Magnetic core-shell nanoparticles for drug delivery by nebulization. J Nanobiotechnol 11:1

    CAS  Google Scholar 

  193. Liang W, Shi X, Deshpande D, Malanga CJ, Rojanasakul Y (1996) Oligonucleotide targeting to alveolar macrophages by mannose receptor-mediated endocytosis. Biochim Biophys Acta Biomembr 1279:227–234

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, Institut Galien Paris-Sud, University of Paris-Sud, Châtenay-Malabry, France

    Nadège Grabowski, Hervé Hillaireau, Juliette Vergnaud & Elias Fattal

Authors
  1. Nadège Grabowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hervé Hillaireau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juliette Vergnaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elias Fattal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elias Fattal .

Editor information

Editors and Affiliations

  1. Institute of Chemical Technology, Department of Pharmaceutical Sciences and Technology, Mumbai, India

    Padma V. Devarajan

  2. National Institute of Pharmaceutical Education and Research (NIPER), Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, Mohali, Punjab, India

    Sanyog Jain

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Controlled Release Society

About this chapter

Cite this chapter

Grabowski, N., Hillaireau, H., Vergnaud, J., Fattal, E. (2015). Evaluation of Lung Toxicity of Biodegradable Nanoparticles. In: Devarajan, P., Jain, S. (eds) Targeted Drug Delivery : Concepts and Design. Advances in Delivery Science and Technology. Springer, Cham. https://doi.org/10.1007/978-3-319-11355-5_22

Download citation

Publish with us

Policies and ethics

Search

Navigation