Skip to main content
SpringerLink
Log in

Pharmacokinetic Properties of Nanomaterials

  • Protocol
Nanomaterials in Pharmacology

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Nanomaterials are a class of materials with unique properties owing to their submicron size. Their possible application as delivery systems for bioactive compounds has been extensively studied for decades. Successful use depends on how well their pharmacokinetics can be controlled after administration into the body. There is plenty of experimental data on the tissue distribution of nanomaterials, but it is still premature to design nanomaterials optimally for the delivery of bioactive compounds. In this chapter, the basic pharmacokinetic properties of nanomaterials, including their interactions with the body, are summarized, followed by a description of some of the challenges for their targeted delivery.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303:1818–1822

    Article  CAS  PubMed  Google Scholar 

  2. Samad A, Sultana Y, Aqil M (2007) Liposomal drug delivery systems: an update review. Curr Drug Deliv 4:297–305

    Article  CAS  PubMed  Google Scholar 

  3. Zhang L, Gu FX, Chan JM et al (2008) Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther 83:761–769

    Article  CAS  PubMed  Google Scholar 

  4. Théry C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579

    PubMed  Google Scholar 

  5. Iero M, Valenti R, Huber V et al (2008) Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15:80–88

    Article  CAS  PubMed  Google Scholar 

  6. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA et al (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A 107:6328–6333

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Takahashi Y, Nishikawa M, Shinotsuka H et al (2013) Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection. J Biotechnol 165:77–84

    Article  CAS  PubMed  Google Scholar 

  8. Desai MP, Labhasetwar V, Amidon GL et al (1996) Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13:1838–1845

    Article  CAS  PubMed  Google Scholar 

  9. Okada H (1997) One- and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate. Adv Drug Deliv Rev 28:43–70

    Article  CAS  PubMed  Google Scholar 

  10. Sethi R, Sanfilippo N (2009) Six-month depot formulation of leuprorelin acetate in the treatment of prostate cancer. Clin Interv Aging 4:259–267

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Nishikawa M, Takakura Y, Hashida M (2005) Theoretical considerations involving the pharmacokinetics of plasmid DNA. Adv Drug Deliv Rev 57:675–688

    Article  CAS  PubMed  Google Scholar 

  12. Takakura Y, Mahato RI, Hashida M (1998) Extravasation of macromolecules. Adv Drug Deliv Rev 34:93–108

    Article  CAS  PubMed  Google Scholar 

  13. Cleaver O, Melton DA (2003) Endothelial signaling during development. Nat Med 9:661–668

    Article  CAS  PubMed  Google Scholar 

  14. Aird WC (2007) Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res 100:158–173

    Article  CAS  PubMed  Google Scholar 

  15. Aird WC (2007) Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res 100:174–190

    Article  CAS  PubMed  Google Scholar 

  16. Rippe B, Rosengren BI, Carlsson O et al (2002) Transendothelial transport: the vesicle controversy. J Vasc Res 39:375–390

    Article  CAS  PubMed  Google Scholar 

  17. Mehta D, Malik AB (2006) Signaling mechanisms regulating endothelial permeability. Physiol Rev 86:279–367

    Article  CAS  PubMed  Google Scholar 

  18. Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153:198–205

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Hobbs SK, Monsky WL, Yuan F et al (1998) Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci U S A 95:4607–4612

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Maeda H, Wu J, Sawa T, Matsumura Y et al (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284

    Article  CAS  PubMed  Google Scholar 

  21. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392

    CAS  PubMed  Google Scholar 

  22. Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56:1649–1659

    Article  CAS  PubMed  Google Scholar 

  23. Brenner BM, Hostetter TH, Humes HD (1978) Glomerular permselectivity: barrier function based on discrimination of molecular size and charge. Am J Physiol 234:F455–F460

    CAS  PubMed  Google Scholar 

  24. Maack T, Johnson V, Kau ST et al (1979) Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review. Kidney Int 16:251–270

    Article  CAS  PubMed  Google Scholar 

  25. Stevens LA, Coresh J, Greene T et al (2006) Assessing kidney function – measured and estimated glomerular filtration rate. N Engl J Med 354:2473–2483

    Article  CAS  PubMed  Google Scholar 

  26. Wolburg H, Lippoldt A (2002) Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol 38:323–337

    Article  CAS  PubMed  Google Scholar 

  27. Abbott NJ, Patabendige AA, Dolman DE et al (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37:13–25

    Article  CAS  PubMed  Google Scholar 

  28. Lockman PR, Mumper RJ, Khan MA et al (2002) Nanoparticle technology for drug delivery across the blood-brain barrier. Drug Dev Ind Pharm 28:1–13

    Article  CAS  PubMed  Google Scholar 

  29. Rapoport SI (2000) Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications. Cell Mol Neurobiol 20:217–230

    Article  CAS  PubMed  Google Scholar 

  30. Opanasopit P, Nishikawa M, Hashida M (2002) Factors affecting drug and gene delivery: effects of interaction with blood components. Crit Rev Ther Drug Carrier Syst 19:191–233

    Article  CAS  PubMed  Google Scholar 

  31. Chonn A, Semple SC, Cullis PR (1982) Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes. J Biol Chem 267:18759–18765

    Google Scholar 

  32. Cullis PR, Chonn A, Semple SC (1998) Interactions of liposomes and lipid-based carrier systems with blood proteins: Relation to clearance behaviour in vivo. Adv Drug Deliv Rev 32:3–17

    Article  PubMed  Google Scholar 

  33. Devine DV, Wong K, Serrano K et al (1994) Liposome-complement interactions in rat serum: implications for liposome survival studies. Biochim Biophys Acta 1191:43–51

    Article  CAS  PubMed  Google Scholar 

  34. Zelphati O, Uyechi LS, Barron LG et al (1998) Effect of serum components on the physico-chemical properties of cationic lipid/oligonucleotide complexes and on their interactions with cells. Biochim Biophys Acta 1390:119–133

    Article  CAS  PubMed  Google Scholar 

  35. Sakurai F, Nishioka T, Saito H et al (2001) Interaction between DNA-cationic liposome complexes and erythrocytes is an important factor in systemic gene transfer via the intravenous route in mice: the role of the neutral helper lipid. Gene Ther 8:677–686

    Article  CAS  PubMed  Google Scholar 

  36. De Smedt SC, Demeester J, Hennink WE (2000) Cationic polymer based gene delivery systems. Pharm Res 17:113–126

    Article  PubMed  Google Scholar 

  37. Zhang S, Zhao B, Jiang H et al (2007) Cationic lipids and polymers mediated vectors for delivery of siRNA. J Control Release 123:1–10

    Article  CAS  PubMed  Google Scholar 

  38. Morille M, Passirani C, Vonarbourg A et al (2008) Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials 29:3477–3496

    Article  CAS  PubMed  Google Scholar 

  39. Semple SC, Akinc A, Chen J et al (2010) Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 28:172–176

    Article  CAS  PubMed  Google Scholar 

  40. Dams ET, Laverman P, Oyen WJ et al (2000) Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J Pharmacol Exp Ther 292:1071–1079

    CAS  PubMed  Google Scholar 

  41. Ishida T, Kiwada H (2008) Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int J Pharm 354:56–62

    Article  CAS  PubMed  Google Scholar 

  42. Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102

    Article  CAS  PubMed  Google Scholar 

  43. Wu J, Nantz MH, Zern MA (2002) Targeting hepatocytes for drug and gene delivery: emerging novel approaches and applications. Front Biosci 7:d717–d725

    Article  CAS  PubMed  Google Scholar 

  44. Nishikawa M (2005) Development of cell-specific targeting systems for drugs and genes. Biol Pharm Bull 28:195–200

    Article  CAS  PubMed  Google Scholar 

  45. Takakura Y, Fujita T, Hashida M et al (1990) Disposition characteristics of macromolecules in tumor-bearing mice. Pharm Res 7:339–346

    Article  CAS  PubMed  Google Scholar 

  46. Ashwell G, Morell AG (1974) The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol 41:99–128

    CAS  PubMed  Google Scholar 

  47. Hashida M, Nishikawa M, Yamashita F et al (2001) Cell-specific delivery of genes with glycosylated carriers. Adv Drug Deliv Rev 52:187–196

    Article  CAS  PubMed  Google Scholar 

  48. Kozarsky KF, Donahee MH, Rigotti A et al (1997) Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 387:414–417

    Article  CAS  PubMed  Google Scholar 

  49. Kingwell BA, Chapman MJ, Kontush A et al (2014) HDL-targeted therapies: progress, failures and future. Nat Rev Drug Discov 13:445–464

    Article  CAS  PubMed  Google Scholar 

  50. Nishida K, Mihara K, Takino T et al (1991) Hepatic disposition characteristics of electrically charged macromolecules in rat in vivo and in the perfused liver. Pharm Res 8:437–444

    Article  CAS  PubMed  Google Scholar 

  51. Nishikawa M, Takakura Y, Hashida M (1996) Pharmacokinetic evaluation of polymeric carriers. Adv Drug Delivery Rev 21:135–155

    Article  CAS  Google Scholar 

  52. Takakura Y, Hashida M (1996) Macromolecular carrier systems for targeted drug delivery: pharmacokinetic considerations on biodistribution. Pharm Res 13:820–831

    Article  CAS  PubMed  Google Scholar 

  53. Berenguer M (2008) Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin. J Hepatol 49:274–287

    Article  CAS  PubMed  Google Scholar 

  54. Jevsevar S, Kunstelj M, Porekar VG (2010) PEGylation of therapeutic proteins. Biotechnol J 5:113–128

    Article  CAS  PubMed  Google Scholar 

  55. Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 55(10):1261–1277

    Article  CAS  PubMed  Google Scholar 

  56. Fujita T, Nishikawa M, Tamaki C et al (1992) Targeted delivery of human recombinant superoxide dismutase by chemical modification with mono- and polysaccharide derivatives. J Pharmacol Exp Ther 263:971–978

    CAS  PubMed  Google Scholar 

  57. Shiah JG, Dvorák M, Kopecková P et al (2001) Biodistribution and antitumour efficacy of long-circulating N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates in nude mice. Eur J Cancer 37:131–139

    Article  CAS  PubMed  Google Scholar 

  58. Kaneda Y, Tsutsumi Y, Yoshioka Y et al (2004) The use of PVP as a polymeric carrier to improve the plasma half-life of drugs. Biomaterials 25:3259–3266

    Article  CAS  PubMed  Google Scholar 

  59. Moghimi SM, Szebeni J (2003) Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res 42:463–478

    Article  CAS  PubMed  Google Scholar 

  60. Alexis F, Pridgen E, Molnar LK et al (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Barenholz Y (2012) Doxil® – the first FDA-approved nano-drug: lessons learned. J Control Release 160:117–134

    Article  CAS  PubMed  Google Scholar 

  62. Nishiyama N, Kataoka K (2006) Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery. Pharmacol Ther 112(3):630–648

    Article  CAS  PubMed  Google Scholar 

  63. Müller RH, Maassen S, Weyhers H et al (1996) Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407. J Drug Target 4:161–170

    Article  PubMed  Google Scholar 

  64. Takeuchi H, Kojima H, Yamamoto H et al (2000) Polymer coating of liposomes with a modified polyvinyl alcohol and their systemic circulation and RES uptake in rats. J Control Release 68:195–205

    Article  CAS  PubMed  Google Scholar 

  65. Metselaar JM, Bruin P, de Boer LW et al (2003) A novel family of l-amino acid-based biodegradable polymer-lipid conjugates for the development of long-circulating liposomes with effective drug-targeting capacity. Bioconjug Chem 14:1156–1164

    Article  CAS  PubMed  Google Scholar 

  66. Peer D, Park EJ, Morishita Y et al (2008) Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 319:627–630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Morschhauser F, Illidge T, Huglo D et al (2007) Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood 110:54–58

    Article  CAS  PubMed  Google Scholar 

  68. Nishikawa M, Miyazaki C, Yamashita F et al (1995) Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties. Am J Physiol 268:G849–G856

    CAS  PubMed  Google Scholar 

  69. Remy JS, Kichler A, Mordvinov V et al (1995) Targeted gene transfer into hepatoma cells with lipopolyamine-condensed DNA particles presenting galactose ligands: a stage toward artificial viruses. Proc Natl Acad Sci U S A 92:1744–1748

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Zanta MA, Boussif O, Adib A et al (1997) In vitro gene delivery to hepatocytes with galactosylated polyethylenimine. Bioconjug Chem 8:839–844

    Article  CAS  PubMed  Google Scholar 

  71. Nishikawa M, Takemura S, Takakura Y et al (1998) Targeted delivery of plasmid DNA to hepatocytes in vivo: optimization of the pharmacokinetics of plasmid DNA/galactosylated poly(l-lysine) complexes by controlling their physicochemical properties. J Pharmacol Exp Ther 287:408–415

    CAS  PubMed  Google Scholar 

  72. Yabe Y, Nishikawa M, Tamada A et al (1999) Targeted delivery and improved therapeutic potential of catalase by chemical modification: combination with superoxide dismutase derivatives. J Pharmacol Exp Ther 289:1176–1184

    CAS  PubMed  Google Scholar 

  73. Sato A, Takagi M, Shimamoto A et al (2007) Small interfering RNA delivery to the liver by intravenous administration of galactosylated cationic liposomes in mice. Biomaterials 28:1434–1442

    Article  CAS  PubMed  Google Scholar 

  74. Connolly DT, Townsend RR, Kawaguchi K et al (1982) Binding and endocytosis of cluster glycosides by rabbit hepatocytes. Evidence for a short-circuit pathway that does not lead to degradation. J Biol Chem 257:939–945

    CAS  PubMed  Google Scholar 

  75. Rensen PC, van Leeuwen SH, Sliedregt LA et al (2004) Design and synthesis of novel N-acetylgalactosamine-terminated glycolipids for targeting of lipoproteins to the hepatic asialoglycoprotein receptor. J Med Chem 47:5798–5808

    Article  CAS  PubMed  Google Scholar 

  76. Akinc A, Querbes W, De S et al (2010) Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol Ther 18:1357–1364

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan

    Makiya Nishikawa Ph.D.

Authors
  1. Makiya Nishikawa Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Makiya Nishikawa Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA

    Zheng-Rong Lu

  2. Laboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan

    Shinji Sakuma

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Nishikawa, M. (2016). Pharmacokinetic Properties of Nanomaterials. In: Lu, ZR., Sakuma, S. (eds) Nanomaterials in Pharmacology. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3121-7_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3121-7_12

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3120-0

  • Online ISBN: 978-1-4939-3121-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation