Skip to main content

Advertisement

Log in

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

  • Expert Review
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

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.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

REFERENCES

  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. Beal MF, Lang AE, Ludolph AC. Neudegenerative diseases: neurobiology, pathogenesis and therapeutics. Cambridge: Cambridge University Press; 2005.

    Book  Google Scholar 

  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. Whalley K. Neurodegenerative disease: undoing aggregation. Nat Rev Neurosci. 2008;9:83.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  6. Burridge S. Neurodegenerative diseases: novel route to neuroprotection. Nat Rev Drug Discov. 2012;11:906–7.

    Article  PubMed  CAS  Google Scholar 

  7. Waldmeier PC, Tatton WG. Interrupting apoptosis in neurodegenerative disease: potential for effective therapy? Drug Discov Today. 2004;9(5):210–8.

    Article  PubMed  CAS  Google Scholar 

  8. Fernandes C, Soni U, Patravale V. Nano-interventions for neurodegenerative disorders. Pharmacol Res. 2010;62:166–78.

    Article  PubMed  CAS  Google Scholar 

  9. Re F, Gregori M, Masserini M. Nanotechnology for neurodegenerative disorders. Nanomed Nanotech Biol Med. 2012; (Suppl 1):S51-S58.

  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.

    Article  PubMed  CAS  Google Scholar 

  11. Nowacek A, Gendelman E. NanoART, neuroAIDS and CNS drug delivery. Nanomedicine (Lond). 2009;4(5):557–74.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  16. Poole CP, Owens FJ. Introduction to nanotechnology. New Jersey: Wiley; 2003.

    Google Scholar 

  17. Vo-Dinh T. Nanotechnology in biology and medicine: methods, devices, and applications. Boca Raton: CRC Press Taylor & Francis Group; 2007.

    Book  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  20. Leucuta SE. Nanotechnology for delivery of drugs and biomedical applications. Curr Clin Pharmacol. 2010;5(4):257–80.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  22. Jain KK. Nanomedicine: application of nanobiotechnology in medical practice. Med Princ Pract. 2008;17(2):89–101.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  24. Singh S. Nanomedicine-nanoscale drugs and delivery systems. J Nanosci Nanotechnol. 2010;10(12):7906–18.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  26. Manish G, Sharma V. Targeted drug delivery system: a review. Res J Chem Sci. 2011;1(2):135–8.

    Google Scholar 

  27. Petrak K. Nanotechnology and site-targeted drug delivery. J Biomater Sci Polym Ed. 2006;17(11):1209–19.

    Article  PubMed  CAS  Google Scholar 

  28. Paulo CS, Pires das Neves R, Ferreira LS. Nanoparticles for intracellular-targeted drug delivery. Nanotechnology. 2011;22(49):1–11.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  30. Srikanth M, Kessler JA. Nanotechnology-novel therapeutics for CNS disorders. Nat Rev Neurol. 2012;8(6):307–18.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  34. Urquhart BL, Kim RB. Blood–brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol. 2009;65(11):1063–70.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  37. Potschka H. Targeting the brain–surmounting or bypassing the blood–brain barrier. Handb Exp Pharmacol. 2010;197:411–31.

    Article  PubMed  CAS  Google Scholar 

  38. Pardridge WM. Biopharmaceutical drug targeting to the brain. J Drug Target. 2010;18(3):157–67.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  55. Eskici G, Axelsen PH. Copper and oxidative stress in the pathogenesis of Alzheimer’s disease. Biochemistry. 2012;51(32):6289–311.

    Article  PubMed  CAS  Google Scholar 

  56. Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012;148(6):1204–22.

    Article  PubMed  CAS  Google Scholar 

  57. Mohamed T, Rao PP. Alzheimer’s disease: emerging trends in small molecule therapies. Curr Med Chem. 2011;18(28):4299–320.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  59. Galimberti D, Scarpini E. Progress in Alzheimer’s disease. J Neurol. 2012;259(2):201–11.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. Elsabahy M, Wooley KL. Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev. 2012;41(7):2545–61.

    Article  PubMed  CAS  Google Scholar 

  63. Mozafari MR. Nanoliposomes: preparation and analysis. Methods Mol Biol. 2010;605:29–50.

    Article  PubMed  CAS  Google Scholar 

  64. Hardy J. Alzheimer’s disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis. 2006;9:151–3.

    PubMed  CAS  Google Scholar 

  65. Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256:184–5.

    Article  PubMed  CAS  Google Scholar 

  66. Selkoe DJ. The molecular pathology of Alzheimer’s disease. Neuron. 1991;6:487–98.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  69. Smith MA. Oxidative stress and iron imbalance in Alzheimer disease: howrust became the fuss! J Alzheimers Dis. 2006;9:305–8.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  74. Soto C. Plaque busters: strategies to inhibit amyloid formation in Alzheimer’s disease. Mol Med Today. 1999;5:343–50.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  91. Fahn S. Levodopa in the treatment of Parkinson’s disease. J Neural Transm Suppl. 2006;71:1–15.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  103. Imran M, Mahmood S. An overview of human prion diseases. Virol J. 2011;8:1–9.

    Article  Google Scholar 

  104. Lloyd S, Mead S, Collinge J. Genetics of prion disease. Top Curr Chem. 2011;305:1–22.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  111. Monteiro-Riviere NA, Lang TC. Nanotoxicology: characterization, dosing and health effects. New York: Informa Health Care USA, Inc; 2007.

    Book  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  120. Win-Shwe TT, Fujimaki H. Nanoparticles and neurotoxicity. Int J Mol Sci. 2011;12:6267–80.

    Article  PubMed  CAS  Google Scholar 

  121. Thassu D, Deleers M, Pathak Y. Nanoparticulate Drug Delivery Systems. New York: Informa Healthcare USA, Inc.; 2007.

    Book  Google Scholar 

  122. Sharma HS, Sharma A. Recent Perspectives on Nanoneuroprotection & Nanoneurotoxicity. CNS Neurol Disord Drug Target. 2012;11(1):1–2.

    Article  Google Scholar 

  123. Hu YL, Gao JQ. Potential neurotoxicity of nanoparticles. Int J Pharm. 2010;94(1–2):115–21.

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS AND DISCLOSURES

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sibel Bozdağ Pehlivan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bozdağ Pehlivan, S. Nanotechnology-Based Drug Delivery Systems for Targeting, Imaging and Diagnosis of Neurodegenerative Diseases. Pharm Res 30, 2499–2511 (2013). https://doi.org/10.1007/s11095-013-1156-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-013-1156-7

KEY WORDS

Navigation