Advertisement

Pharmaceutical Research

, Volume 30, Issue 10, pp 2499–2511 | Cite as

Nanotechnology-Based Drug Delivery Systems for Targeting, Imaging and Diagnosis of Neurodegenerative Diseases

  • Sibel Bozdağ Pehlivan
Expert Review

ABSTRACT

Neurodegenerative disorders are becoming prevalent with the increasing age of the general population. A number of difficulties have emerged for the potential treatment of neurodegenerative diseases, as these disorders may be multi systemic in nature. Due to limitations regarding the blood brain barrier (BBB) structure, efflux pumps and metabolic enzyme expression, conventional drug delivery systems do not provide efficient therapy for neurodegenerative disorders. Nanotechnology can offer impressive improvement of the neurodegenerative disease treatment by using bio-engineered systems interacting with biological systems at a molecular level. This review focuses on the nano-enabled system applications for the treatment and diagnosis of neurodegenerative diseases, in particular Alzheimer’s, Parkinson’s and Prion diseases.

KEY WORDS

blood brain barrier nano-enabled delivery systems nanotechnology neurodegenerative diseases 

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This paper does not reflect any financial, commercial, or other relationship between the author and any other party.

REFERENCES

  1. 1.
    Ellison D, Love S, Chimelli L, Harding BN, Lowe J, Vinters HV. Neuropathology: A reference text of CNS pathology. London: Mosby; 2004.Google Scholar
  2. 2.
    Beal MF, Lang AE, Ludolph AC. Neudegenerative diseases: neurobiology, pathogenesis and therapeutics. Cambridge: Cambridge University Press; 2005.CrossRefGoogle Scholar
  3. 3.
    Cacciatore I, Baldassarre L, Fornasari E, Mollica A, Pinnen F. Recent advances in the treatment of neurodegenerative diseases based on GSH delivery systems. Oxide Med Cell Longev. 2012. doi: 10.1155/2012/240146.Google Scholar
  4. 4.
    Whalley K. Neurodegenerative disease: undoing aggregation. Nat Rev Neurosci. 2008;9:83.CrossRefGoogle Scholar
  5. 5.
    Bartus RT. On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp Neurol. 2000;163(2):495–529.PubMedCrossRefGoogle Scholar
  6. 6.
    Burridge S. Neurodegenerative diseases: novel route to neuroprotection. Nat Rev Drug Discov. 2012;11:906–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Waldmeier PC, Tatton WG. Interrupting apoptosis in neurodegenerative disease: potential for effective therapy? Drug Discov Today. 2004;9(5):210–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Fernandes C, Soni U, Patravale V. Nano-interventions for neurodegenerative disorders. Pharmacol Res. 2010;62:166–78.PubMedCrossRefGoogle Scholar
  9. 9.
    Re F, Gregori M, Masserini M. Nanotechnology for neurodegenerative disorders. Nanomed Nanotech Biol Med. 2012; (Suppl 1):S51-S58.Google Scholar
  10. 10.
    Modi G, Pillay V, Choonara YE. Advances in the treatment of neurodegenerative disorders employing nanotechnology. Ann N Y Acad Sci. 2010;1184:154–72.PubMedCrossRefGoogle Scholar
  11. 11.
    Nowacek A, Gendelman E. NanoART, neuroAIDS and CNS drug delivery. Nanomedicine (Lond). 2009;4(5):557–74.CrossRefGoogle Scholar
  12. 12.
    Modi G, Pillay V, Choonara YE, Ndesendo VM, du Toit LC, Naidoo D. Nanotechnological applications for the treatment of neurodegenerative disorders. Prog Neurobiol. 2009;88(4):272–85.PubMedCrossRefGoogle Scholar
  13. 13.
    Barchet T, Amiji MM. Challenges and opportunities in CNS delivery of therapeutics for neurodegenerative diseases. Expert Opin Drug Deliv. 2009;6(3):211–25.PubMedCrossRefGoogle Scholar
  14. 14.
    Spuch C, Navarro C. Liposomes for targeted delivery of active agents against neurodegenerative diseases (Alzheimer’s Disease and Parkinson’s Disease). J Drug Deliv. 2011;2011:1–12.CrossRefGoogle Scholar
  15. 15.
    Awad RA. Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson’s disease. World J Gastroenterol. 2011;17(46):5035–48.PubMedCrossRefGoogle Scholar
  16. 16.
    Poole CP, Owens FJ. Introduction to nanotechnology. New Jersey: Wiley; 2003.Google Scholar
  17. 17.
    Vo-Dinh T. Nanotechnology in biology and medicine: methods, devices, and applications. Boca Raton: CRC Press Taylor & Francis Group; 2007.CrossRefGoogle Scholar
  18. 18.
    Cho Y, Borgens RB. Polymer and nano-technology applications for repair and reconstruction of the central nervous system. Exp Neurol. 2012;233(1):126–44.PubMedCrossRefGoogle Scholar
  19. 19.
    Mahmood M, Casciano D, Xu Y, Biris AS. Engineered nanostructural materials for application in cancer biology and medicine. J Appl Toxicol. 2012;32(1):10–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Leucuta SE. Nanotechnology for delivery of drugs and biomedical applications. Curr Clin Pharmacol. 2010;5(4):257–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Silva GA. Nanotechnology approaches to crossing the blood–brain barrier and drug delivery to the CNS. BMC Neurosci. 2008;9 Suppl 3:S1–4.CrossRefGoogle Scholar
  22. 22.
    Jain KK. Nanomedicine: application of nanobiotechnology in medical practice. Med Princ Pract. 2008;17(2):89–101.PubMedCrossRefGoogle Scholar
  23. 23.
    Liu Y, Tan J, Thomas A, Ou-Yang D, Muzykantov VR. The shape of things to come: importance of design in nanotechnology for drug delivery. Ther Deliv. 2012;3(2):181–94.PubMedCrossRefGoogle Scholar
  24. 24.
    Singh S. Nanomedicine-nanoscale drugs and delivery systems. J Nanosci Nanotechnol. 2010;10(12):7906–18.PubMedCrossRefGoogle Scholar
  25. 25.
    Koo OM, Rubinstein I, Onyuksel H. Role of nanotechnology in targeted drug delivery and imaging:a concise review. Nanomed Nanotech Biol Med. 2005;1:193–212.CrossRefGoogle Scholar
  26. 26.
    Manish G, Sharma V. Targeted drug delivery system: a review. Res J Chem Sci. 2011;1(2):135–8.Google Scholar
  27. 27.
    Petrak K. Nanotechnology and site-targeted drug delivery. J Biomater Sci Polym Ed. 2006;17(11):1209–19.PubMedCrossRefGoogle Scholar
  28. 28.
    Paulo CS, Pires das Neves R, Ferreira LS. Nanoparticles for intracellular-targeted drug delivery. Nanotechnology. 2011;22(49):1–11.CrossRefGoogle Scholar
  29. 29.
    Gagliardi M, Bardi G, Bifone A. Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS. Ther Deliv. 2012;3(7):875–87.PubMedCrossRefGoogle Scholar
  30. 30.
    Srikanth M, Kessler JA. Nanotechnology-novel therapeutics for CNS disorders. Nat Rev Neurol. 2012;8(6):307–18.PubMedCrossRefGoogle Scholar
  31. 31.
    De Rosa G, Salzano G, Caraglia M, Abbruzzese A. Nanotechnologies: a strategy to overcome blood–brain barrier. Curr Drug Metab. 2012;13(1):61–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Mangas-Sanjuan V, González-Alvarez M, Gonzalez-Alvarez I, Bermejo M. Drug penetration across the blood–brain barrier: an overview. Ther Deliv. 2010;1(4):535–62.PubMedCrossRefGoogle Scholar
  33. 33.
    Tucker IG, Yang L, Mujoo H. Delivery of drugs to the brain via the blood brain barrier using colloidal carriers. J Microencapsul. 2012;29(5):475–86.PubMedCrossRefGoogle Scholar
  34. 34.
    Urquhart BL, Kim RB. Blood–brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol. 2009;65(11):1063–70.PubMedCrossRefGoogle Scholar
  35. 35.
    Geldenhuys WJ, Allen DD, Bloomquist JR. Novel models for assessing blood–brain barrier drug permeation. Expert Opin Drug Metab Toxicol. 2012;8(6):647–53.PubMedCrossRefGoogle Scholar
  36. 36.
    Orthmann A, Fichtner I, Zeisig R. Improving the transport of chemotherapeutic drugs across the blood–brain barrier. Expert Rev Clin Pharmacol. 2011;4(4):477–90.PubMedCrossRefGoogle Scholar
  37. 37.
    Potschka H. Targeting the brain–surmounting or bypassing the blood–brain barrier. Handb Exp Pharmacol. 2010;197:411–31.PubMedCrossRefGoogle Scholar
  38. 38.
    Pardridge WM. Biopharmaceutical drug targeting to the brain. J Drug Target. 2010;18(3):157–67.PubMedCrossRefGoogle Scholar
  39. 39.
    Alam MI, Beg S, Samad A, Baboota S, Kohli K, Ali J, et al. Strategy for effective brain drug delivery. Eur J Pharm Sci. 2010;40(5):385–403.PubMedCrossRefGoogle Scholar
  40. 40.
    Burov S, Leko M, Dorosh M, Dobrodumov A, Veselkina O. Creatinyl amino acids: new hybrid compounds with neuroprotective activity. J Pept Sci. 2011;17(9):620–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Liu Y, Hu Y, Guo Y, Ma H, Li J, Jiang C. Targeted imaging of activated caspase-3 in the central nervous system by a dual functional nano-device. J Control Release. 2012;163(2):203–10.PubMedCrossRefGoogle Scholar
  42. 42.
    Prades R, Guerrero S, Araya E, Molina C, Salas E, Zurita E, et al. Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor. Biomaterials. 2012;33(29):7194–205.PubMedCrossRefGoogle Scholar
  43. 43.
    Ulbrich K, Hekmatara T, Herbert E, Kreuter J. Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood–brain barrier (BBB). Eur J Pharm Biopharm. 2009;71(2):251–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Zhang P, Hu L, Yin Q, Zhang Z, Feng L, Li Y. Transferrin-conjugated polyphosphoester hybrid micelle loading paclitaxel for brain-targeting delivery: synthesis, preparation and in vivo evaluation. J Control Release. 2012;159(3):429–34.PubMedCrossRefGoogle Scholar
  45. 45.
    Chang J, Paillard A, Passirani C, Morille M, Benoit JP, Betbeder D, et al. Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells. Pharm Res. 2012;29(6):1495–505.PubMedCrossRefGoogle Scholar
  46. 46.
    Kuo YC, Lin PI, Wang CC. Targeting nevirapine delivery across human brain microvascular endothelial cells using transferrin-grafted poly(lactide-co-glycolide) nanoparticles. Nanomedicine (Lond). 2011;6(6):1011–26.CrossRefGoogle Scholar
  47. 47.
    Prabhakar K, Afzal SM, Kumar PU, Rajanna A, Kishan V. Brain delivery of transferrin coupled indinavir submicron lipid emulsions–pharmacokinetics and tissue distribution. Colloids Surf B Biointerfaces. 2011;86(2):305–13.PubMedCrossRefGoogle Scholar
  48. 48.
    Jain A, Chasoo G, Singh SK, Saxena AK, Jain SK. Transferrin-appended PEGylated nanoparticles for temozolomide delivery to brain: in vitro characterisation. J Microencapsul. 2011;28(1):21–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Yemişci M, Gürsoy-Özdemir Y, Caban S, Bodur E, Capan Y, Dalkara T. Transport of a caspase inhibitor across the blood–brain barrier by chitosan nanoparticles. Methods Enzymol. 2012;508:253–69.PubMedCrossRefGoogle Scholar
  50. 50.
    Shao K, Huang R, Li J, Han L, Ye L, Lou J, et al. Angiopep-2 modified PE-PEG based polymeric micelles for amphotericin B delivery targeted to the brain. J Control Release. 2010;147(1):118–26.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhao M, Chang J, Fu X, Liang C, Liang S, Yan R, et al. Nano-sized cationic polymeric magnetic liposomes significantly improves drug delivery to the brain in rats. J Drug Target. 2012;20(5):416–21.PubMedCrossRefGoogle Scholar
  52. 52.
    Dakwar GR, Abu Hammad I, Popov M, Linder C, Grinberg S, Heldman E, et al. Delivery of proteins to the brain by bolaamphiphilic nano-sized vesicles. J Control Release. 2012;160(2):315–21.PubMedCrossRefGoogle Scholar
  53. 53.
    Agarwal A, Agrawal H, Tiwari S, Jain S, Agrawal GP. Cationic ligand appended nanoconstructs: a prospective strategy for brain targeting. Int J Pharm. 2011;421(1):189–201.PubMedCrossRefGoogle Scholar
  54. 54.
    Di Carlo M, Giacomazza D, San Biagio PL. Alzheimer’s disease: biological aspects, therapeutic perspectives and diagnostic tools. J Phys Condens Matter. 2012;24(24):1–17.CrossRefGoogle Scholar
  55. 55.
    Eskici G, Axelsen PH. Copper and oxidative stress in the pathogenesis of Alzheimer’s disease. Biochemistry. 2012;51(32):6289–311.PubMedCrossRefGoogle Scholar
  56. 56.
    Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012;148(6):1204–22.PubMedCrossRefGoogle Scholar
  57. 57.
    Mohamed T, Rao PP. Alzheimer’s disease: emerging trends in small molecule therapies. Curr Med Chem. 2011;18(28):4299–320.PubMedCrossRefGoogle Scholar
  58. 58.
    Loef M, Walach H. Copper and iron in Alzheimer’s disease: a systematic review and its dietary implications. Br J Nutr. 2012;107(1):7–19.PubMedCrossRefGoogle Scholar
  59. 59.
    Galimberti D, Scarpini E. Progress in Alzheimer’s disease. J Neurol. 2012;259(2):201–11.PubMedCrossRefGoogle Scholar
  60. 60.
    Di Stefano A, Lannitelli A, Laserra S, Sozio P. Drug delivery strategies for Alzheimer’s disease treatment. Expert Opin Drug Deliv. 2011;8(5):581–603.PubMedCrossRefGoogle Scholar
  61. 61.
    Mathew A, Fukuda T, Nagaoka Y, Hasumura T, Morimoto H, Yoshida Y, et al. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS One. 2012;7(3):1–10.Google Scholar
  62. 62.
    Elsabahy M, Wooley KL. Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev. 2012;41(7):2545–61.PubMedCrossRefGoogle Scholar
  63. 63.
    Mozafari MR. Nanoliposomes: preparation and analysis. Methods Mol Biol. 2010;605:29–50.PubMedCrossRefGoogle Scholar
  64. 64.
    Hardy J. Alzheimer’s disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis. 2006;9:151–3.PubMedGoogle Scholar
  65. 65.
    Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256:184–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Selkoe DJ. The molecular pathology of Alzheimer’s disease. Neuron. 1991;6:487–98.PubMedCrossRefGoogle Scholar
  67. 67.
    Crouch PJ, Barnham KJ, Bush AI, White AR. Therapeutic treatments for Alzheimer’s disease based on metal bioavailability. Drug News Perspect. 2006;19:469–74.PubMedCrossRefGoogle Scholar
  68. 68.
    Liu G, Garrett MR, Men P, Zhu X, Perry G, Smith MA. Nanoparticle and other metal chelation therapeutics in Alzheimer disease. Biochim Biophys Acta. 2005;1741:246–52.PubMedCrossRefGoogle Scholar
  69. 69.
    Smith MA. Oxidative stress and iron imbalance in Alzheimer disease: howrust became the fuss! J Alzheimers Dis. 2006;9:305–8.PubMedGoogle Scholar
  70. 70.
    Mufamadi MS, Choonara YE, Kumar P, Modi G, Naidoo D, Ndesendo VM, et al. Surface-engineered nanoliposomes by chelating ligands for modulating the neurotoxicity associated with β-Amyloid aggregates of Alzheimer’s disease. Pharm Res. 2012;29(11):3075–89.PubMedCrossRefGoogle Scholar
  71. 71.
    Liu G, Men P, Kudo W, Perry G, Smith MA. Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease. Neurosci Lett. 2009;455(3):187–90.PubMedCrossRefGoogle Scholar
  72. 72.
    Lopez OL, Rabin BS, Huff FJ, Rezek D, Reinmuth OM. Serum autoantibodies in patients with Alzheimer’s disease and vascular dementia and in nondemented control subjects. Stroke. 1992;23:1078–83.PubMedCrossRefGoogle Scholar
  73. 73.
    Morgan D, Diamond DM, Gottschall PE, Ugen KE, Dickey C, Hardy J, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature. 2000;408(6815):982–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Soto C. Plaque busters: strategies to inhibit amyloid formation in Alzheimer’s disease. Mol Med Today. 1999;5:343–50.PubMedCrossRefGoogle Scholar
  75. 75.
    Fradinger EA, Monien BH, Urbanc B, Lomakin A, Tan M, Li H, et al. C-terminal peptides coassemble into Abeta42 oligomers and protect neurons against Abeta42-induced neurotoxicity. Proc Natl Acad Sci U S A. 2008;105:14175–80.PubMedCrossRefGoogle Scholar
  76. 76.
    Songjiang Z, Lixiang W. Amyloid-beta associated with chitosan nano-carrier has favorable immunogenicity and permeates the BBB. AAPS PharmSciTech. 2009;10(3):900–5.PubMedCrossRefGoogle Scholar
  77. 77.
    Agyare EK, Curran GL, Ramakrishnan M, Yu CC, Poduslo JF, Kandimalla KK. Development of a smart nano-vehicle to target cerebrovascular amyloid deposits and brain parenchymal plaques observed in Alzheimer’s disease and cerebral amyloid angiopathy. Pharm Res. 2008;25(11):2674–84.PubMedCrossRefGoogle Scholar
  78. 78.
    Poduslo JF, Ramakrishnan M, Holasek SS, Ramirez-Alvarado M, Kandimalla KK, Gilles EJ, et al. In vivo targeting of antibody fragments to the nervous system for Alzheimer’s disease immunotherapy and molecular imaging of amyloid plaques. J Neurochem. 2007;102:420–33.PubMedCrossRefGoogle Scholar
  79. 79.
    Mourtas S, Canovi M, Zona C, Aurilia D, Niarakis A, La Ferla B, et al. Curcumin-decorated nanoliposomes with very high affinity for amyloid-β1-42 peptide. Biomaterials. 2011;32(6):1635–45.PubMedCrossRefGoogle Scholar
  80. 80.
    Re F, Cambianica I, Sesana S, Salvati E, Cagnotto A, Salmona M, et al. Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide. J Biotechnol. 2010;156(4):341–6.PubMedCrossRefGoogle Scholar
  81. 81.
    Fang YP, Tsai YH, Wu PC, Huang YB. Comparison of 5-aminolevulinic acid-encapsulated liposome versus ethosome for skin delivery for photodynamic therapy. Int J Pharm. 2008;356:144–52.PubMedCrossRefGoogle Scholar
  82. 82.
    Mishra D, Mishra PK, Dabadghao S, Dubey V, Nahar M, Jain NK. Comparative evaluation of hepatitis B surface antigen-loaded elastic liposomes and ethosomes for human dendritic cell uptake and immune response. Nanomedicine. 2010;6:110–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Zhao L, Wei MJ, He M, Jin WB, Zhao HS, Yao WF. The effects of tetramethylpyrazine on learning and memory abilities of mice with Alzheimer disease and its possible mechanism. Chin Pharmacol Bull. 2008;24:1088–92.Google Scholar
  84. 84.
    Shi J, Wang Y, Luo G. Ligustrazine phosphate ethosomes for treatment of Alzheimer’s disease, in vitro and in animal model studies. AAPS PharmSciTech. 2012;13(2):485–92.PubMedCrossRefGoogle Scholar
  85. 85.
    Beg S, Samad A, Alam MI, Nazish I. Dendrimers as novel systems for delivery of neuropharmaceuticals to the brain. CNS Neurol Disord Drug Targets. 2011;10(5):576–88.PubMedCrossRefGoogle Scholar
  86. 86.
    Sharma A, Gautam SP, Gupta AK. Surface modified dendrimers: synthesis and characterization for cancer targeted drug delivery. Bioorg Med Chem. 2011;19(11):3341–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Wasiak T, Ionov M, Nieznanski K, Nieznanska H, Klementieva O, Granell M, et al. Phosphorus dendrimers affect Alzheimer’s (Aβ1-28) peptide and MAP-Tau protein aggregation. Mol Pharm. 2012;9(3):458–69.PubMedCrossRefGoogle Scholar
  88. 88.
    Yang X, Zheng R, Cai Y, Liao M, Yuan W, Liu Z. Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats. Int J Nanomedicine. 2012;7:2077–86.PubMedGoogle Scholar
  89. 89.
    Xiang Y, Wu Q, Liang L, Wang X, Wang J, Zhang X, et al. Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting delivery against Parkinson’s disease in the MPTP-induced mice model. J Drug Target. 2012;20(1):67–75.PubMedCrossRefGoogle Scholar
  90. 90.
    Trapani A, De Giglio E, Cafagna D, Denora N, Agrimi G, Cassano T, et al. Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery. Int J Pharm. 2011;419(1–2):296–307.PubMedCrossRefGoogle Scholar
  91. 91.
    Fahn S. Levodopa in the treatment of Parkinson’s disease. J Neural Transm Suppl. 2006;71:1–15.PubMedCrossRefGoogle Scholar
  92. 92.
    Black KJ, Carl JL, Hartlein JM, Warren SL, Hershey T, Perlmutter JS. Rapid intravenous loading of levodopa for human research: clinical results. J Neurosci Methods. 2003;127(1):19–29.PubMedCrossRefGoogle Scholar
  93. 93.
    During MJ, Freese A, Deutch AY, Kibat PG, Sabel BA, Langer R, et al. Biochemical and behavioral recovery in a rodent model of Parkinson’s disease following stereotactic implantation of dopamine-containing liposomes. Exp Neurol. 1992;115(2):193–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Muthuprasanna P, Manisha M, Suriaprabha K, Srinivasa Rao T, Anbu J. Formulation and psychopharmacological evaluation of surfactant modified liposome for parkinsonism disease. Asian J Pharm Clin Res. 2010;3(1):46–54.Google Scholar
  95. 95.
    Esposito E, Fantin M, Marti M, Drechsler M, Paccamiccio L, Mariani P, et al. Solid lipid nanoparticles as delivery systems for bromocriptine. Pharm Res. 2008;25(7):1521–30.PubMedCrossRefGoogle Scholar
  96. 96.
    Zhao Y, Haney MJ, Klyachko NL, Li S, Booth SL, Higginbotham SM, et al. Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles. Nanomedicine (Lond). 2011;6(1):25–42.CrossRefGoogle Scholar
  97. 97.
    Azeem A, Talegaonkar S, Negi LM, Ahmad FJ, Khar RK, Iqbal Z. Oil based nanocarrier system for transdermal delivery of ropinirole: a mechanistic, pharmacokinetic and biochemical investigation. Int J Pharm. 2012;422(1–2):436–44.PubMedCrossRefGoogle Scholar
  98. 98.
    Pillay S, Pillay V, Choonara YE, Naidoo D, Khan RA, du Toit LC, et al. Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain. Int J Pharm. 2009;382(1–2):277–90.PubMedCrossRefGoogle Scholar
  99. 99.
    Rekas A, Lo V, Gadd GE, Cappai R, Yun SI. PAMAM dendrimers as potential agents against fibrillation of alpha-synuclein, a Parkinson’s disease-related protein. Macromol Biosci. 2009;9(3):230–8.PubMedCrossRefGoogle Scholar
  100. 100.
    Malvindi MA, Di Corato R, Curcio A, Melisi D, Rimoli MG, Tortiglione C, et al. Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine. Nanoscale. 2011;3(12):5110–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Hu K, Shi Y, Jiang W, Han J, Huang S, Jiang X. Lactoferrin conjugated PEG-PLGA nanoparticles for brain delivery: preparation, characterization and efficacy in Parkinson’s disease. Int J Pharm. 2011;415(1–2):273–83.PubMedCrossRefGoogle Scholar
  102. 102.
    Marandi Y, Farahi N, Sadeghi A, Sadeghi-Hashjin G. Prion diseases - current theories and potential therapies: a brief review. Folia Neuropathol. 2012;50(1):46–9.PubMedGoogle Scholar
  103. 103.
    Imran M, Mahmood S. An overview of human prion diseases. Virol J. 2011;8:1–9.CrossRefGoogle Scholar
  104. 104.
    Lloyd S, Mead S, Collinge J. Genetics of prion disease. Top Curr Chem. 2011;305:1–22.PubMedCrossRefGoogle Scholar
  105. 105.
    Klajnert B, Cortijo-Arellano M, Bryszewska M, Cladera J. Influence of heparin and dendrimers on the aggregation of two amyloid peptides related to Alzheimer’s and prion diseases. Biochem Biophys Res Commun. 2006;339(2):577–82.PubMedCrossRefGoogle Scholar
  106. 106.
    Skaat H, Belfort G, Margel S. Synthesis and characterization of fluorinated magnetic core-shell nanoparticles for inhibition of insulin amyloid fibril formation. Nanotechnology. 2009;20(22):1–9.CrossRefGoogle Scholar
  107. 107.
    Sousa F, Mandal S, Garrovo C, Astolfo A, Bonifacio A, Latawiec D, et al. Functionalized gold nanoparticles: a detailed in vivo multimodal microscopic brain distribution study. Nanoscale. 2010;2(12):2826–34.PubMedCrossRefGoogle Scholar
  108. 108.
    Calvo P, Gouritin B, Brigger I, Lasmezas C, Deslys J, Williams A, et al. PEGylated polycyanoacrylate nanoparticles as vector for drug delivery in prion diseases. J Neurosci Methods. 2001;111(2):151–5.PubMedCrossRefGoogle Scholar
  109. 109.
    Kim HR, Andrieux K, Gil S, Taverna M, Chacun H, Desmaële D, et al. Translocation of poly(ethylene glycolco- hexadecyl)cyanoacrylate nanoparticles into rat brain endothelial cells:role of apolipoproteins in receptor-mediated endocytosis. Biomacromolecules. 2007;8:793–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Ulbrich K, Hekmatara T, Herbert E, Kreuter J. Transferrin- and transferrinreceptor-antibody-modified nanoparticles enable drug delivery across the blood–brain barrier (BBB). Eur J Pharm Biopharm. 2009;71:251–6.PubMedCrossRefGoogle Scholar
  111. 111.
    Monteiro-Riviere NA, Lang TC. Nanotoxicology: characterization, dosing and health effects. New York: Informa Health Care USA, Inc; 2007.CrossRefGoogle Scholar
  112. 112.
    Jia G, Wang H, Yan L, Wang X, Pei R, Yan T, et al. Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol. 2005;39(5):1378–83.PubMedCrossRefGoogle Scholar
  113. 113.
    Wang J, Sun P, Bao Y, Liu J, An L. Cytotoxicity of single-walled carbon nanotubes on PC12 cells. Toxicol In Vitro. 2011;25(1):242–50.PubMedCrossRefGoogle Scholar
  114. 114.
    Deng X, Luan Q, Chen W, Wang Y, Wu M, Zhang H, et al. Nanosized zinc oxide particles induce neural stem cell apoptosis. Nanotechnology. 2009;20(11):1–7.CrossRefGoogle Scholar
  115. 115.
    Hussain SM, Javorina AK, Schrand AM, Duhart HM, Ali SF, Schlager JJ. The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. Toxicol Sci. 2006;92(2):456–63.PubMedCrossRefGoogle Scholar
  116. 116.
    Long TC, Saleh N, Tilton RD, Lowry GV, Veronesi B. Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity. Environ Sci Technol. 2006;40(14):4346–52.PubMedCrossRefGoogle Scholar
  117. 117.
    Pisanic 2nd TR, Blackwell JD, Shubayev VI, Fiñones RR, Jin S. Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. Biomaterials. 2007;28(16):2572–81.PubMedCrossRefGoogle Scholar
  118. 118.
    Zhang QL, Li MQ, Ji JW, Gao FP, Bai R, Chen CY, et al. In vivo toxicity of nano-alumina on mice neurobehavioral profiles and the potential mechanisms. Int J Immunopathol Pharmacol. 2011;24(1 Suppl):23S–9S.PubMedGoogle Scholar
  119. 119.
    Wu J, Wang C, Sun J, Xue Y. Neurotoxicity of silica nanoparticles: brain localization and dopaminergic neurons damage pathways. ACS Nano. 2011;5(6):4476–89.PubMedCrossRefGoogle Scholar
  120. 120.
    Win-Shwe TT, Fujimaki H. Nanoparticles and neurotoxicity. Int J Mol Sci. 2011;12:6267–80.PubMedCrossRefGoogle Scholar
  121. 121.
    Thassu D, Deleers M, Pathak Y. Nanoparticulate Drug Delivery Systems. New York: Informa Healthcare USA, Inc.; 2007.CrossRefGoogle Scholar
  122. 122.
    Sharma HS, Sharma A. Recent Perspectives on Nanoneuroprotection & Nanoneurotoxicity. CNS Neurol Disord Drug Target. 2012;11(1):1–2.CrossRefGoogle Scholar
  123. 123.
    Hu YL, Gao JQ. Potential neurotoxicity of nanoparticles. Int J Pharm. 2010;94(1–2):115–21.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Faculty of Pharmacy, Department of Pharmaceutical TechnologyHacettepe UniversityAnkaraTurkey

Personalised recommendations