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Nanoparticle Functionalization for Brain Targeting Drug Delivery and Diagnostic

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Handbook of Nanoparticles

Abstract

Nanobiotechnology has been demonstrated to be an efficient tool for targeted therapy as well as diagnosis, with particular emphasis on brain tumor and neurodegenerative diseases. On this regard, the aim of this chapter is focused on engineered nanoparticles targeted to the brain, so that they have the ability to overcome the blood–brain barrier (BBB) and enter the brain tissue. Firstly, it highlighted the difficulty of physically active molecules and colloidal carriers to overcome BBB, which is an impediment for the treatment of several brain diseases; then, the use of nanoparticles as advantageous carriers to cross the BBB and achieve brain, and their functionalization strategies are described; and finally the delivery of nanoparticles to the target moiety, as diagnostics or therapeutics. Therefore, this chapter is focused on how the nanoparticle surface may be functionalized for drug delivery and diagnostics. Furthermore, it is also mentioned that some BBB targets were already used as transport mediators to central nervous system by functionalization on nanoparticles. It summarizes the nanoparticles potential in therapeutics and molecular targeting to BBB, and also an approach of the nanoparticle-mediated drug transport across the BBB, where nanoparticles take advantage of physiological receptor-mediated transport processes.

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References

  1. N.J. Abbott, Blood–brain barrier structure and function and the challenges for CNS drug delivery. J. Inherit. Metab. Dis. 36, 1–13 (2013)

    Google Scholar 

  2. N.J. Abbott, A.A. Patabendige, D.E. Dolman, S.R. Yusof, D.J. Begley, Structure and function of the blood–brain barrier. Neurobiol. Dis. 37(1), 13–25 (2010)

    Article  Google Scholar 

  3. M.I. Alam, S. Beg, A. Samad, S. Baboota, K. Kohli, J. Ali, A. Ahuja, M. Akbar, Strategy for effective brain drug delivery. Eur. J. Pharm. Sci. 40(5), 385–403 (2010)

    Article  Google Scholar 

  4. D.D. Allen, P.R. Lockman, K.E. Roder, L.P. Dwoskin, P.A. Crooks, Active transport of high-affinity choline and nicotine analogs into the central nervous system by the blood–brain barrier choline transporter. J. Pharmacol. Exp. Ther. 304(3), 1268–1274 (2003)

    Article  Google Scholar 

  5. L. Araujo, R. Löbenberg, J. Kreuter, Influence of the surfactant concentration on the body distribution of nanoparticles. J. Drug Target. 6(5), 373–385 (1999)

    Article  Google Scholar 

  6. A. Armulik, G. Genové, M. Mäe, M.H. Nisancioglu, E. Wallgard, C. Niaudet, L. He, J. Norlin, P. Lindblom, K. Strittmatter, Pericytes regulate the blood–brain barrier. Nature 468(7323), 557–561 (2010)

    Article  Google Scholar 

  7. D.J. Begley, ABC transporters and the blood–brain barrier. Curr. Pharm. Des. 10(12), 1295–1312 (2004)

    Article  Google Scholar 

  8. S. Bhaskar, F. Tian, T. Stoeger, W. Kreyling, J.M. de la Fuente, V. Grazu, P. Borm, G. Estrada, V. Ntziachristos, D. Razansky, Multifunctional nanocarriers for diagnostics, drug delivery and targeted treatment across blood–brain barrier: perspectives on tracking and neuroimaging. Part. Fibre Toxicol. 7, 3 (2010)

    Article  Google Scholar 

  9. A. Bolhassani, Potential efficacy of cell-penetrating peptides for nucleic acid and drug delivery in cancer. Biochim. Biophys. Acta 1816(2), 232–246 (2011)

    Google Scholar 

  10. I. Brigger, J. Morizet, G. Aubert, H. Chacun, M.-J. Terrier-Lacombe, P. Couvreur, Poly(ethylene glycol)-coated hexadecylcyanoacrylate nanospheres display a combined effect for brain tumor targeting. J. Pharmacol. Exp. Ther. 303(3), 928–936 (2002)

    Article  Google Scholar 

  11. F.L. Cardoso, D. Brites, M.A. Brito, Looking at the blood–brain barrier: molecular anatomy and possible investigation approaches. Brain Res. Rev. 64(2), 328–363 (2010)

    Article  Google Scholar 

  12. Y. Chen, L. Liu, Modern methods for delivery of drugs across the blood–brain barrier. Adv. Drug Deliv. Rev. 64(7), 640–665 (2012)

    Article  Google Scholar 

  13. Y. Chen, G. Dalwadi, H.A. Benson, Drug delivery across the blood–brain barrier. Curr. Drug Deliv. 1(4), 361–376 (2004)

    Article  Google Scholar 

  14. Y.K. Choi, K.-W. Kim, Blood-neural barrier: its diversity and coordinated cell-to-cell communication. Genesis 10, 11 (2008)

    Google Scholar 

  15. P. Couvreur, B. Kante, L. Grislain, M. Roland, P. Speiser, Toxicity of polyalkylcyanoacrylate nanoparticles II: doxorubicin-loaded nanoparticles. J. Pharm. Sci. 71, 790–792 (1982)

    Article  Google Scholar 

  16. S. Dauchy, F. Dutheil, R.J. Weaver, F. Chassoux, C. Daumas-Duport, P.O. Couraud, J.M. Scherrmann, I. De Waziers, X. Declèves, ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood–brain barrier. J. Neurochem. 107(6), 1518–1528 (2008)

    Article  Google Scholar 

  17. A. De Boer, P. Gaillard, Drug targeting to the brain. Annu. Rev. Pharmacol. Toxicol. 47, 323–355 (2007)

    Article  Google Scholar 

  18. M. Dean, Y. Hamon, G. Chimini, The human ATP-binding cassette (ABC) transporter superfamily. J. Lipid Res. 42(7), 1007–1017 (2001)

    Google Scholar 

  19. B. Dehouck, L. Fenart, M.-P. Dehouck, A. Pierce, G. Torpier, R. Cecchelli, A new function for the LDL receptor: transcytosis of LDL across the blood–brain barrier. J. Cell Biol. 138(4), 877–889 (1997)

    Article  Google Scholar 

  20. K.R. Duffy, W.M. Pardridge, Blood–brain barrier transcytosis of insulin in developing rabbits. Brain Res. 420, 32–38 (1987)

    Article  Google Scholar 

  21. K.R. Duffy, W.M. Pardridge, R.G. Rosenfeld, Human blood–brain barrier insulin-like growth factor receptor. Metabolism 37(2), 136–140 (1988)

    Article  Google Scholar 

  22. M. Fisher, Pericyte signaling in the neurovascular unit. Stroke 40(3 Suppl. 1), S13–S15 (2009)

    Article  Google Scholar 

  23. M. Fisher, M. Abramov, A. Van Aerschot, D. Xu, R.L. Juliano, P. Herdewijn, Inhibition of MDR1 expression with altritol-modified siRNAs. Nucleic Acids Res. 35(4), 1064–1074 (2007)

    Article  Google Scholar 

  24. R. Gabathuler, Approaches to transport therapeutic drugs across the blood–brain barrier to treat brain diseases. Neurobiol. Dis. 37(1), 48–57 (2010)

    Article  Google Scholar 

  25. P.J. Gaillard, A. Brink, A.G. de Boer, Diphtheria toxin receptor-targeted brain drug delivery. Int. Congr. Ser. 1277, 185–198 (2005)

    Article  Google Scholar 

  26. P.J. Gaillard, C.C. Appeldoorn, J. Rip, R. Dorland, S.M. van der Pol, G. Kooij, H.E. de Vries, A. Reijerkerk, Enhanced brain delivery of liposomal methylprednisolone improved therapeutic efficacy in a model of neuroinflammation. J. Control. Release 164(3), 364–369 (2012)

    Article  Google Scholar 

  27. A. Gessner, A. Lieske, B.R. Paulke, R.H. Muller, Influence of surface charge density on protein adsorption on polymeric nanoparticles: analysis by two-dimensional electrophoresis. Eur. J. Pharm. Biopharm. 54(2), 165–170 (2002)

    Article  Google Scholar 

  28. S. Gill, R. Löbenberg, T. Ku, S. Azarmi, W. Roa, E.J. Prenner, Nanoparticles: characteristics, mechanisms of action, and toxicity in pulmonary drug delivery – a review. J. Biomed. Nanotechnol. 3(2), 107–119 (2007)

    Article  Google Scholar 

  29. J.L. Gilmore, X. Yi, L. Quan, A.V. Kabanov, Novel nanomaterials for clinical neuroscience. J. Neuroimmune Pharmacol. 3(2), 83–94 (2008)

    Article  Google Scholar 

  30. T.M. Goppert, R.H. Muller, Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: comparison of plasma protein adsorption patterns. J. Drug Target. 13(3), 179–187 (2005)

    Article  Google Scholar 

  31. A. Gulyaev, S. Gelperina, I. Skidan, A. Antropov, G. Kivman, J. Kreuter, Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles. Pharm. Res. 16, 1564–1569 (1999)

    Article  Google Scholar 

  32. A. Hartz, B. Bauer, Regulation of ABC transporters at the blood–brain barrier: new targets for CNS therapy. Mol. Interv. 10(5), 293 (2010)

    Article  Google Scholar 

  33. F. Hervé, N. Ghinea, J.-M. Scherrmann, CNS delivery via adsorptive transcytosis. AAPS J. 10(3), 455–472 (2008)

    Article  Google Scholar 

  34. H. Hillaireau, P. Couvreur, Nanocarriers’ entry into the cell: relevance to drug delivery. Cell. Mol. Life Sci. 66(17), 2873–2896 (2009)

    Article  Google Scholar 

  35. G.H. Huynh, D.F. Deen, F.C. Szoka Jr., Barriers to carrier mediated drug and gene delivery to brain tumors. J. Control. Release 110(2), 236–259 (2006)

    Article  Google Scholar 

  36. R.K. Jain, Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J. Control. Release 74, 7–25 (2001)

    Article  Google Scholar 

  37. K. Jain, Role of nanotechnology in developing new therapies for diseases of the nervous system. Nanomedicine 1(1), 9–12 (2006)

    Article  Google Scholar 

  38. K.K. Jain, The Handbook of Nanomedicine (Springer, Dordrecht, 2012)

    Book  Google Scholar 

  39. S.W. Jones, R. Christison, K. Bundell, C.J. Voyce, S.M. Brockbank, P. Newham, M.A. Lindsay, Characterisation of cell-penetrating peptide-mediated peptide delivery. Br. J. Pharmacol. 145(8), 1093–1102 (2005)

    Article  Google Scholar 

  40. L. Juillerat-Jeanneret, The targeted delivery of cancer drugs across the blood–brain barrier: chemical modifications of drugs or drug-nanoparticles? Drug Discov. Today 13(23–24), 1099–1106 (2008)

    Article  Google Scholar 

  41. I.P. Kaur, R. Bhandari, S. Bhandari, V. Kakkar, Potential of solid lipid nanoparticles in brain targeting. J. Control. Release 127(2), 97–109 (2008)

    Article  Google Scholar 

  42. M. Lindgren, U. Langel, Classes and prediction of cell-penetrating peptides. Methods Mol. Biol. 683, 3–19 (2011)

    Article  Google Scholar 

  43. C.A. Lipinski, Lead-and drug-like compounds: the rule-of-five revolution. Drug. Discov. Today Technol. 1(4), 337–341 (2004)

    Article  Google Scholar 

  44. C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23(1), 3–25 (1997)

    Article  Google Scholar 

  45. L. Liu, K. Guo, J. Lu, S.S. Venkatraman, D. Luo, K.C. Ng, E.-A. Ling, S. Moochhala, Y.-Y. Yang, Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG–TAT for drug delivery across the blood–brain barrier. Biomaterials 29(10), 1509–1517 (2008)

    Article  Google Scholar 

  46. P. Lockman, R. Mumper, M. Khan, D. Allen, Nanoparticle technology for drug delivery across the blood–brain barrier. Drug Dev. Ind. Pharm. 28(1), 1–13 (2002)

    Article  Google Scholar 

  47. P.R. Lockman, J.M. Koziara, R.J. Mumper, D.D. Allen, Nanoparticle surface charges alter blood–brain barrier integrity and permeability. J. Drug Target. 12(9–10), 635–641 (2004)

    Article  Google Scholar 

  48. H. Maeda, J. Fang, T. Inutsuka, Y. Kitamoto, Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. Int. Immunopharmacol. 3(3), 319–328 (2003)

    Article  Google Scholar 

  49. S. Majumdar, T.J. Siahaan, Peptide-mediated targeted drug delivery. Med. Res. Rev. 32(3), 637–658 (2012)

    Article  Google Scholar 

  50. Y.M. Matsumura, H. Maeda, 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 (1986)

    Google Scholar 

  51. K. Michaelis, M.M. Hoffmann, S. Dreis, E. Herbert, R.N. Alyautdin, M. Michaelis, J. Kreuter, K. Langer, Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain. J. Pharmacol. Exp. Ther. 317(3), 1246–1253 (2006)

    Article  Google Scholar 

  52. T. Moos, E.H. Morgan, Transferrin and transferrin receptor function in brain barrier systems. Cell. Mol. Neurobiol. 20(1), 77–95 (2000)

    Article  Google Scholar 

  53. S.K. Murthy, Nanoparticles in modern medicine: state of the art and future challenges. Int. J. Nanomedicine 2(2), 129–141 (2007)

    Google Scholar 

  54. K. Nagpal, S.K. Singh, D.N. Mishra, Drug targeting to brain: a systematic approach to study the factors, parameters and approaches for prediction of permeability of drugs across BBB. Expert Opin. Drug Deliv. 10, 927–955 (2013)

    Article  Google Scholar 

  55. A. Nunes, K.T. Al-Jamal, K. Kostarelos, Therapeutics, imaging and toxicity of nanomaterials in the central nervous system. J. Control. Release 161(2), 290–306 (2012)

    Article  Google Scholar 

  56. W.M. Pardridge, Drug and gene delivery to the brain: the vascular route. Neuron 36(4), 555–558 (2002)

    Article  Google Scholar 

  57. W.M. Pardridge, Blood–brain barrier drug targeting: the future of brain drug development. Mol. Interv. 3(2), 90 (2003)

    Article  Google Scholar 

  58. W.M. Pardridge, The blood–brain barrier: bottleneck in brain drug development. NeuroRx 2(1), 3–14 (2005)

    Article  Google Scholar 

  59. W.M. Pardridge, Blood–brain barrier delivery. Drug Discov. Today 12(1–2), 54–61 (2007)

    Article  Google Scholar 

  60. W.M. Pardridge, J. Eisenberg, J. Yang, Human blood–brain barrier transferrin receptor. Metabolism 36(9), 892–895 (1987)

    Article  Google Scholar 

  61. W.M. Pardridge, J.L. Buciak, P.M. Friden, Selective transport of an anti-transferrin receptor antibody through the blood–brain barrier in vivo. J. Pharmacol. Exp. Ther. 259(1), 66–70 (1991)

    Google Scholar 

  62. M. Ribeiro, M. Castanho, I. Serrano, In vitro blood–brain barrier models-latest advances and therapeutic applications in a chronological perspective. Mini Rev. Med. Chem. 10(3), 263–271 (2010)

    Article  Google Scholar 

  63. A. Saleh, M. Schroeter, C. Jonkmanns, H. Hartung, U. Mödder, S. Jander, In vivo MRI of brain inflammation in human ischaemic stroke. Brain 127, 1670–1677 (2004)

    Article  Google Scholar 

  64. S. Santaguida, D. Janigro, M. Hossain, E. Oby, E. Rapp, L. Cucullo, Side by side comparison between dynamic versus static models of blood? brain barrier in vitro: a permeability study. Brain Res. 1109(1), 1–13 (2006)

    Article  Google Scholar 

  65. H. Santos, L. Bimbo, J. das Neves, B. Sarmento, Nanoparticulate targeted drug delivery using peptides and proteins, in Nanomedicine: Technologies and Applications, ed. by T.J. Webster (Woodhead Publishing Limited, Cambridge, 2012)

    Google Scholar 

  66. K. Tahara, Y. Miyazaki, Y. Kawashima, J. Kreuter, H. Yamamoto, Brain targeting with surface-modified poly(d, l-lactic-co-glycolic acid) nanoparticles delivered via carotid artery administration. Eur. J. Pharm. Biopharm. 77(1), 84–88 (2011). doi:10.1016/j.ejpb.2010.11.002

    Article  Google Scholar 

  67. J.E. Vance, H. Hayashi, Formation and function of apolipoprotein E-containing lipoproteins in the nervous system. Biochim. Biophys. Acta 1801(8), 806–818 (2010)

    Article  Google Scholar 

  68. J.S. Weinstein, C.G. Varallyay, E. Dosa, S. Gahramanov, B. Hamilton, W.D. Rooney, L.L. Muldoon, E.A. Neuwelt, Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review. J. Cereb. Blood Flow Metab. 30(1), 15–35 (2010)

    Article  Google Scholar 

  69. N. Weiss, F. Miller, S. Cazaubon, P.-O. Couraud, The blood–brain barrier in brain homeostasis and neurological diseases. Biochim. Biophys. Acta 1788(4), 842–857 (2009)

    Article  Google Scholar 

  70. B. Wilson, M.K. Samanta, K. Santhi, K.P. Kumar, N. Paramakrishnan, B. Suresh, Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles. Eur. J. Pharm. Biopharm. 70(1), 75–84 (2008). doi:10.1016/j.ejpb.2008.03.009

    Article  Google Scholar 

  71. J.L. Winer, P.E. Kim, M. Law, C.Y. Liu, M.L. Apuzzo, Visualizing the future: enhancing neuroimaging with nanotechnology. World Neurosurg. 75(5–6), 626–637 (2011)

    Article  Google Scholar 

  72. S. Wohlfart, S. Gelperina, J. Kreuter, Transport of drugs across the blood–brain barrier by nanoparticles. J. Control. Release 161(2), 264–273 (2012)

    Article  Google Scholar 

  73. H. Xin, L. Chen, J. Gu, X. Ren, Z. Wei, J. Luo, Y. Chen, X. Jiang, X. Sha, X. Fang, Enhanced anti-glioblastoma efficacy by PTX-loaded PEGylated poly(varepsilon-caprolactone) nanoparticles: in vitro and in vivo evaluation. Int. J. Pharm. 402(1–2), 238–247 (2010)

    Article  Google Scholar 

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Acknowledgment

Maria João Gomes gratefully acknowledges Fundação para a Ciência e a Tecnologia (FCT), Portugal, for financial support (grant SFRH/BD/90404/2012). This work was partially supported by a grant from FCT (PTDC/SAU-FAR/112277/2009).

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Authors and Affiliations

  1. INEB, Institute of Biomedical Engineering, University of Porto, Porto, Portugal

    Maria João Gomes, Bárbara Mendes & Bruno Sarmento

  2. Faculty of Engineering, University of Porto, Porto, Portugal

    Bárbara Mendes

  3. Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark

    Susana Martins

  4. IINFACTS, Department of Pharmaceutical Sciences, Instituto Superior de Ciências da Saúde-Norte, Gandra, Portugal

    Bruno Sarmento

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  1. Maria João Gomes
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  2. Bárbara Mendes
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Correspondence to Bruno Sarmento .

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Editors and Affiliations

  1. Department of Materials Engineering, Tarbiat Modares University, Tehran, Iran

    Mahmood Aliofkhazraei

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Gomes, M.J., Mendes, B., Martins, S., Sarmento, B. (2016). Nanoparticle Functionalization for Brain Targeting Drug Delivery and Diagnostic. In: Aliofkhazraei, M. (eds) Handbook of Nanoparticles. Springer, Cham. https://doi.org/10.1007/978-3-319-15338-4_42

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