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Advances in Personalized Nanotherapeutics pp 157–185Cite as

CNS Drug Delivery for Diseases Eradication: An Overview

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Abstract

Central nervous system (CNS) diseases lead to severe disability and account for considerable amount of health burden globally making them one of the most devastating diseases affecting the mankind. Though new drugs to eradicate CNS diseases are much warranted, drug development in this field is going at snail’s pace due to potential limitation of low success rate in clinical trials. Therapeutic delivery to the brain offers superior challenge to scientific community because of the presence of blood brain barrier (BBB), the lipophilic barrier which hampers the entry of foreign substances into brain and drug efflux transporters which prevents drug accumulation in CSF (Cerebro spinal fluid). Further it is assumed that BBB permeability and brain pharmacokinetics alters with pathological condition which further complicates the drug delivery. In view of this altered physiology, scientists have designed some pharmaceutically active formulations of drug molecules which can lodge in brain because of their altered lipophilicity, selective permeability or ligand based targeting. Such delivery options enhance the efficient delivery of active therapeutic molecules to the target of interest without showing any side effects. Such site directed target delivery also ensures improved brain pharmacokinetics of the compounds. This book chapter offers information about myriad range of CNS diseases; unmet needs in their management and several novel methods of CNS directed delivery options for therapeutics to alleviate those nervous disorders with maximum efficacy. In particular by realizing the emergence of nano technology and nano medicine, we have discussed nano technology based formulations and their potential importance for CNS delivery in detail.

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References

  1. Stefan LR. Psychological training and counseling for the increase of personnel well-being and flight safety. Rev Air Force Acad. 2015;3(30):149. doi:10.19062/1842-9238.2015.13.3.26.

    Article  Google Scholar 

  2. Organization WH. The world health report 2001: mental health: new understanding, new hope. Geneva: World Health Organization; 2001.

    Google Scholar 

  3. Saxena S, Funk M, Chisholm D. Comprehensive mental health action plan 2013–2020. East Mediterr Health J. 2015;21:461.

    Article  CAS  PubMed  Google Scholar 

  4. Lu Y. Rural-urban migration and health: evidence from longitudinal data in Indonesia. Soc Sci Med. 2010;70(3):412–9.

    Article  PubMed  Google Scholar 

  5. Pangalos MN, Schechter LE, Hurko O. Drug development for CNS disorders: strategies for balancing risk and reducing attrition. Nat Rev Drug Discov. 2007;6(7):521–32.

    Article  CAS  PubMed  Google Scholar 

  6. DiMasi JA, Grabowski HG. The cost of biopharmaceutical R&D: is biotech different? Manag Decis Econ. 2007;28(4-5):469–79.

    Article  Google Scholar 

  7. De Smaele E, Ferretti E, Gulino A. MicroRNAs as biomarkers for CNS cancer and other disorders. Brain Res. 2010;1338:100–11.

    Article  PubMed  CAS  Google Scholar 

  8. Bicker J, Alves G, Fortuna A, Falcao A. Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review. Eur J Pharm Biopharm. 2014;87(3):409–32.

    Article  CAS  PubMed  Google Scholar 

  9. Hawkins BT, Davis TP. The blood–brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85.

    Article  CAS  PubMed  Google Scholar 

  10. Upadhyay RK. Drug delivery systems, CNS protection, and the blood brain barrier. Biomed Res Int. 2014;2014:1–37.

    Google Scholar 

  11. Nagpal K, Singh SK, Mishra DN. 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. 2013;10(7):927–55.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Petty MA, Lo EH. Junctional complexes of the blood–brain barrier: permeability changes in neuroinflammation. Prog Neurobiol. 2002;68(5):311–23.

    Article  CAS  PubMed  Google Scholar 

  14. Banks WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug deliveryNat Rev Drug Discov, vol. 15; 2016. p. 275–92.

    Google Scholar 

  15. Redzic Z. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS. 2011;8(1):3.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sanchez-Covarrubias L, Slosky LM, Thompson BJ, Davis TP, Ronaldson PT. Transporters at CNS barrier sites: obstacles or opportunities for drug delivery? Curr Pharm Des. 2014;20(10):1422–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.

    Article  CAS  PubMed  Google Scholar 

  18. Genes-Hernandez LI. Development of a microfluidic based microvascular model: towards a complete blood brain barrier (BBB) mimic. 2008. ProQuest

    Google Scholar 

  19. Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K. Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol. 2004;30(7):979–89.

    Article  PubMed  Google Scholar 

  20. Pardridge WM. Drug delivery to the brain. J Cereb Blood Flow Metab. 1997;17(7):713–31.

    Article  CAS  PubMed  Google Scholar 

  21. Pardridge WM. Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv. 2003;3(2):90.

    Article  CAS  PubMed  Google Scholar 

  22. Benita S. Microencapsulation: methods and industrial applications. Boca Raton: CRC; 2005.

    Book  Google Scholar 

  23. Kanwar JR, Sriramoju B, Kanwar RK. Neurological disorders and therapeutics targeted to surmount the blood–brain barrier. Int J Nanomedicine. 2012;7:3259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459–509.

    Article  Google Scholar 

  25. Golde TE. Overcoming translational barriers impeding development of Alzheimer’s disease modifying therapies. J Neurochem. 2016;139:224–36.

    Article  CAS  PubMed  Google Scholar 

  26. Underwood E. Alzheimer’s amyloid theory gets modest boost. Science. 2015;349(6247):464.

    Article  CAS  PubMed  Google Scholar 

  27. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones R, Bullock R, Love S, Neal J. Long term effects of Ab42 immunization in Alzheimer’s disease: immune response, plaque removal and clinical function. Lancet. 2008;372:216–23.

    Article  CAS  PubMed  Google Scholar 

  28. Liu E, Schmidt ME, Margolin R, Sperling R, Koeppe R, Mason NS, Klunk WE, Mathis CA, Salloway S, Fox NC. Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials. Neurology. 2015;85(8):692–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Siemers ER, Friedrich S, Dean RA, Gonzales CR, Farlow MR, Paul SM, DeMattos RB. Safety and changes in plasma and cerebrospinal fluid amyloid β after a single administration of an amyloid β monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol. 2010;33(2):67–73.

    Article  CAS  PubMed  Google Scholar 

  30. Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6(3):131–44.

    Article  CAS  PubMed  Google Scholar 

  31. Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, Kapogiannis D. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology. 2015;85(1):40–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Carroll RT, Bhatia D, Geldenhuys W, Bhatia R, Miladore N, Bishayee A, Sutariya V. Brain-targeted delivery of Tempol-loaded nanoparticles for neurological disorders. J Drug Target. 2010;18(9):665–74.

    Article  CAS  PubMed  Google Scholar 

  33. Sahni JK, Doggui S, Ali J, Baboota S, Dao L, Ramassamy C. Neurotherapeutic applications of nanoparticles in Alzheimer’s disease. J Control Release. 2011;152(2):208–31.

    Article  CAS  PubMed  Google Scholar 

  34. Wang ZH, Wang ZY, Sun CS, Wang CY, Jiang TY, Wang SL. Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain. Biomaterials. 2010;31(5):908–15.

    Article  CAS  PubMed  Google Scholar 

  35. World Health Organization. Global burden of neurological disorders: estimates and projections. In: Neurological disorders: public health challenges. Geneva: WHO Press; 2007. p. 27–39.

    Google Scholar 

  36. Gordon R, Kelley MD. Parkinson’s disease incidence and prevalence; 2000. Parkinsons Disease Foundation

    Google Scholar 

  37. van der Brug MP, Singleton A, Gasser T, Lewis PA. Parkinson’s disease: from human genetics to clinical trials. Sci Transl Med. 2015;7(305):205–20.

    Google Scholar 

  38. Sanchez-Mut JV, Heyn H, Vidal E, Moran S, Sayols S, Delgado-Morales R, Schultz MD, Ansoleaga B, Garcia-Esparcia P, Pons-Espinal M. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns. Transl Psychiatry. 2016;6(1):e718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Atlas D. DopAmide: novel, water-soluble, slow-release l-dihydroxyphenylalanine (l-DOPA) precursor moderates l-DOPA conversion to dopamine and generates a sustained level of dopamine at dopaminergic neurons. CNS Neurosci Ther. 2016;22:461–7.

    Article  CAS  PubMed  Google Scholar 

  40. Shen T, Pu J, Si X, Ye R, Zhang B. An update on potential therapeutic strategies of Parkinson’s disease based on pathogenic mechanisms. Expert review of neurotherapeutics (just-accepted). Expert Rev Neurother. 2016;16(6):711–22.

    Article  CAS  PubMed  Google Scholar 

  41. Pillay V, Choonara YE, Sibeko B, Harilall S-L, Pillay S, Modi G, Iyuke SE, Naidoo D. Polymeric pharmaceutical dosage form in sustained release; 2009. Google Patents

    Google Scholar 

  42. Gendelman HE, Anantharam V, Bronich T, Ghaisas S, Jin H, Kanthasamy AG, Liu X, McMillan J, Mosley RL, Narasimhan B. Nanoneuromedicines for degenerative, inflammatory, and infectious nervous system diseases. Nanomedicine. 2015;11(3):751–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mathers C, Fat DM, Boerma JT. The global burden of disease: 2004 update. Geneva: World Health Organization; 2008.

    Book  Google Scholar 

  44. Carpenter WT, Koenig JI. The evolution of drug development in schizophrenia: past issues and future opportunities. Neuropsychopharmacology. 2008;33(9):2061–79.

    Article  CAS  PubMed  Google Scholar 

  45. Bernard A, Fischer M, Robert W, Buchanan M. Schizophrenia: epidemiology and pathogenesis, vol. 2016. Alphen: Wolters Kluwer; 2016.

    Google Scholar 

  46. Modini M, Tan L, Brinchmann B, Wang M-J, Killackey E, Glozier N, Mykletun A, Harvey SB. Supported employment for people with severe mental illness: systematic review and meta-analysis of the international evidence. Br J Psychiatry. 2016;115:165092.

    Google Scholar 

  47. Commission S. The abandoned illness: a report from the Schizophrenia Commission. London: Rethink Mental Illness; 2012.

    Google Scholar 

  48. Lieberman JA, Perkins D, Belger A, Chakos M, Jarskog F, Boteva K, Gilmore J. The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry. 2001;50(11):884–97.

    Article  CAS  PubMed  Google Scholar 

  49. Addington J, Heinssen R. Prediction and prevention of psychosis in youth at clinical high risk. Annu Rev Clin Psychol. 2012;8:269–89.

    Article  PubMed  Google Scholar 

  50. Lewandowski K, Cohen B, Öngur D. Evolution of neuropsychological dysfunction during the course of schizophrenia and bipolar disorder. Psychol Med. 2011;41(02):225–41.

    Article  CAS  PubMed  Google Scholar 

  51. Moghaddam B, Javitt D. From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology. 2012;37(1):4–15.

    Article  CAS  PubMed  Google Scholar 

  52. Meyer-Lindenberg A, Tost H. Neuroimaging and plasticity in schizophrenia. Restor Neurol Neurosci. 2014;32(1):119–27.

    PubMed  Google Scholar 

  53. Haijma SV, Van Haren N, Cahn W, Koolschijn PCM, Pol HEH, Kahn RS. Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. Schizophr Bull. 2013;39(5):1129–38.

    Article  PubMed  Google Scholar 

  54. Barch DM, Ceaser A. Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cogn Sci. 2012;16(1):27–34.

    Article  PubMed  Google Scholar 

  55. Ting JT, Peça J, Feng G. Functional consequences of mutations in postsynaptic scaffolding proteins and relevance to psychiatric disorders. Annu Rev Neurosci. 2012;35:49–71.

    Article  CAS  PubMed  Google Scholar 

  56. Ripke S, Neale BM, Corvin A, Walters JT, Farh K-H, Holmans PA, Lee P, Bulik-Sullivan B, Collier DA, Huang H. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421.

    Article  CAS  PubMed Central  Google Scholar 

  57. Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E, Palta P, Ruderfer DM. De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014;506(7487):179–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cardiff U, Owen MJ, Sawa A, Mortensen PB. Lancet. 2016;388:86–97.

    Article  Google Scholar 

  59. Bhaskar S, Tian F, Stoeger T, Kreyling W, de la Fuente JM, Grazú V, Borm P, Estrada G, Ntziachristos V, Razansky D. Multifunctional nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging. Part Fibre Toxicol. 2010;7(1):1.

    Article  CAS  Google Scholar 

  60. Miyamoto S, Miyake N, Jarskog L, Fleischhacker W, Lieberman J. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Mol Psychiatry. 2012;17(12):1206–27.

    Article  CAS  PubMed  Google Scholar 

  61. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996;153(3):321.

    Article  CAS  PubMed  Google Scholar 

  62. Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, Thwin SS, Vertrees JE, Liang MH. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011;364(9):842–51.

    Article  CAS  PubMed  Google Scholar 

  63. Pereira JNDS, Tadjerpisheh S, Abed MA, Saadatmand AR, Weksler B, Romero IA, Couraud P-O, Brockmöller J, Tzvetkov MV. The poorly membrane permeable antipsychotic drugs amisulpride and sulpiride are substrates of the organic cation transporters from the SLC22 family. AAPS J. 2014;16(6):1247–58.

    Article  CAS  Google Scholar 

  64. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. 2013;34:119.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Schechter LE, Ring RH, Beyer CE, Hughes ZA, Khawaja X, Malberg JE, Rosenzweig-Lipson S. Innovative approaches for the development of antidepressant drugs: current and future strategies. NeuroRx. 2005;2(4):590–611.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Dale E, Bang-Andersen B, Sánchez C. Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochem Pharmacol. 2015;95(2):81–97.

    Article  CAS  PubMed  Google Scholar 

  67. Haque S, Md S, Sahni JK, Ali J, Baboota S. Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression. J Psychiatr Res. 2014;48(1):1–12.

    Article  PubMed  Google Scholar 

  68. Xie Y, Wang Y, Zhang T, Ren G, Yang Z. Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors. J Biomed Sci. 2012;19(1):1.

    Article  CAS  Google Scholar 

  69. American Heart Association. Heart disease and stroke statistics—at-a-glance. 2015

    Google Scholar 

  70. Mukherjee D, Patil CG. Epidemiology and the global burden of stroke. World Neurosurg. 2011;76(6):S85–90.

    Article  PubMed  Google Scholar 

  71. Jordán J, Ikuta I, Garcia-Garcia J, Calleja S, Segura T. Stroke pathophysiology: management challenges and new treatment advances. J Physiol Biochem. 2007;63(3):261–77.

    Article  PubMed  Google Scholar 

  72. Yun X, Maximov VD, Yu J, Vertegel AA, Kindy MS. Nanoparticles for targeted delivery of antioxidant enzymes to the brain after cerebral ischemia and reperfusion injury. J Cereb Blood Flow Metab. 2013;33(4):583–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-Oncology. 2015;17(suppl 4):iv1–iv62.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM. The epidemiology of glioma in adults: a “state of the science” review. Neuro Oncol. 2014;16:896–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 2007;170(5):1445–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mao H, LeBrun DG, Yang J, Zhu VF, Li M. Deregulated signaling pathways in glioblastoma multiforme: molecular mechanisms and therapeutic targets. Cancer Investig. 2012;30(1):48–56.

    Article  Google Scholar 

  78. Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol. 2006;2(9):494–503.

    Article  PubMed  Google Scholar 

  79. Taylor TE, Furnari FB, Cavenee WK. Targeting EGFR for treatment of glioblastoma: molecular basis to overcome resistance. Curr Cancer Drug Targets. 2012;12(3):197–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Huse JT, Holland EC. Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 2010;10(5):319–31.

    Article  CAS  PubMed  Google Scholar 

  81. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5(3):161–71.

    Article  CAS  PubMed  Google Scholar 

  82. Chen H, Qin Y, Zhang Q, Jiang W, Tang L, Liu J, He Q. Lactoferrin modified doxorubicin-loaded procationic liposomes for the treatment of gliomas. Eur J Pharm Sci. 2011;44(1):164–73.

    Article  CAS  PubMed  Google Scholar 

  83. Fillebeen C, Descamps L, Dehouck M-P, Fenart L, Benaïssa M, Spik G, Cecchelli R, Pierce A. Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. J Biol Chem. 1999;274(11):7011–7.

    Article  CAS  PubMed  Google Scholar 

  84. Fu Y, An N, Li K, Zheng Y, Liang A. Chlorotoxin-conjugated nanoparticles as potential glioma-targeted drugs. J Neuro-Oncol. 2012;107(3):457–62.

    Article  CAS  Google Scholar 

  85. Choe G, Park JK, Jouben-Steele L, Kremen TJ, Liau LM, Vinters HV, Cloughesy TF, Mischel PS. Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype. Clin Cancer Res. 2002;8(9):2894–901.

    CAS  PubMed  Google Scholar 

  86. Gao H, Yang Z, Zhang S, Cao S, Shen S, Pang Z, Jiang X. Ligand modified nanoparticles increases cell uptake, alters endocytosis and elevates glioma distribution and internalization. Sci Rep. 2013;3:2534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Shevtsov M, Parr M, Ryzhov V, Zemtsova E, Arbenin AY, Ponomareva A, Smirnov V, Multhoff G. Zero-valent Fe confined mesoporous silica nanocarriers (Fe (0)@ MCM-41) for targeting experimental orthotopic glioma in rats. Sci Rep. 2016;6:29247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Pathan SA, Iqbal Z, Zaidi S, Talegaonkar S, Vohra D, Jain GK, Azeem A, Jain N, Lalani JR, Khar RK. CNS drug delivery systems: novel approaches. Recent Pat Drug Deliv Formul. 2009;3(1):71–89.

    Article  CAS  PubMed  Google Scholar 

  89. Raghavan R, Brady ML, Rodríguez-Ponce MI, Hartlep A, Pedain C, Sampson JH. Convection-enhanced delivery of therapeutics for brain disease, and its optimization. Neurosurg Focus. 2006;20(4):E12.

    Article  PubMed  Google Scholar 

  90. Allard E, Passirani C, Benoit J-P. Convection-enhanced delivery of nanocarriers for the treatment of brain tumors. Biomaterials. 2009;30(12):2302–18.

    Article  CAS  PubMed  Google Scholar 

  91. Ay I, Francis JW, Brown RH. VEGF increases blood–brain barrier permeability to Evans blue dye and tetanus toxin fragment C but not adeno-associated virus in ALS mice. Brain Res. 2008;1234:198–205.

    Article  CAS  PubMed  Google Scholar 

  92. Choi M, Ku T, Chong K, Yoon J, Choi C. Minimally invasive molecular delivery into the brain using optical modulation of vascular permeability. Proc Natl Acad Sci. 2011;108(22):9256–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Aryal M, Arvanitis CD, Alexander PM, McDannold N. Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system. Adv Drug Deliv Rev. 2014;72:94–109.

    Article  CAS  PubMed  Google Scholar 

  94. Andresen V, Alexander S, Heupel W-M, Hirschberg M, Hoffman RM, Friedl P. Infrared multiphoton microscopy: subcellular-resolved deep tissue imaging. Curr Opin Biotechnol. 2009;20(1):54–62.

    Article  CAS  PubMed  Google Scholar 

  95. Treat LH, McDannold N, Vykhodtseva N, Zhang Y, Tam K, Hynynen K. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer. 2007;121(4):901–7.

    Article  CAS  PubMed  Google Scholar 

  96. Stockwell J, Abdi N, Lu X, Maheshwari O, Taghibiglou C. Novel central nervous system drug delivery systems. Chem Biol Drug Des. 2014;83(5):507–20.

    Article  CAS  PubMed  Google Scholar 

  97. Dvir E, Elman A, Simmons D, Shapiro I, Duvdevani R, Dahan A, Hoffman A, Friedman JE. DP-155, a lecithin derivative of indomethacin, is a novel nonsteroidal antiinflammatory drug for analgesia and Alzheimer’s disease therapy. CNS Drug Rev. 2007;13(2):260–77.

    Article  CAS  PubMed  Google Scholar 

  98. Vytla D, Combs-Bachmann RE, Hussey AM, McCarron ST, McCarthy DS, Chambers JJ. Prodrug approaches to reduce hyperexcitation in the CNS. Adv Drug Deliv Rev. 2012;64(7):666–85.

    Article  CAS  PubMed  Google Scholar 

  99. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders M, Endou H. Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002;61(4):729–37.

    Article  CAS  PubMed  Google Scholar 

  100. Salameh F, Karaman D, Mecca G, Scrano L, Bufo SA, Karaman R. Prodrugs targeting the central nervous system (CNS). World J Pharm Pharm Sci. 2015;4(8):208–37.

    CAS  Google Scholar 

  101. Thakral S, Mehta R. Fullerenes: an introduction and overview of their biological properties. Indian J Pharm Sci. 2006;68(1):13–6.

    Article  CAS  Google Scholar 

  102. Tykhomyrov AA, Nedzvetsky VS, Klochkov VK, Andrievsky GV. Nanostructures of hydrated C 60 fullerene (C 60 HyFn) protect rat brain against alcohol impact and attenuate behavioral impairments of alcoholized animals. Toxicology. 2008;246(2):158–65.

    Article  CAS  PubMed  Google Scholar 

  103. Dugan LL, Turetsky DM, Du C, Lobner D, Wheeler M, Almli CR, Shen CK-F, Luh T-Y, Choi DW, Lin T-S. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci. 1997;94(17):9434–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Lin AM-Y, Fang S-F, Lin S-Z, Chou C-K, Luh T-Y, Ho L-T. Local carboxyfullerene protects cortical infarction in rat brain. Neurosci Res. 2002;43(4):317–21.

    Article  CAS  PubMed  Google Scholar 

  105. Yin J-J, Lao F, Fu PP, Wamer WG, Zhao Y, Wang PC, Qiu Y, Sun B, Xing G, Dong J. The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. Biomaterials. 2009;30(4):611–21.

    Article  CAS  PubMed  Google Scholar 

  106. Wong HL, Wu XY, Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev. 2012;64(7):686–700.

    Article  CAS  PubMed  Google Scholar 

  107. Patel T, Zhou J, Piepmeier JM, Saltzman WM. Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev. 2012;64(7):701–5.

    Article  CAS  PubMed  Google Scholar 

  108. Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J. Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res. 1997;14(3):325–8.

    Article  CAS  PubMed  Google Scholar 

  109. Kurakhmaeva KB, Djindjikhashvili IA, Petrov VE, Balabanyan VU, Voronina TA, Trofimov SS, Kreuter J, Gelperina S, Begley D, Alyautdin RN. Brain targeting of nerve growth factor using poly (butyl cyanoacrylate) nanoparticles. J Drug Target. 2009;17(8):564–74.

    Article  CAS  PubMed  Google Scholar 

  110. Aliautdin R, Petrov V, Ivanov A, Kreuter J, Kharkevich D. Transport of the hexapeptide dalargin across the hemato-encephalic barrier into the brain using polymer nanoparticles. Eksp Klin Farmakol. 1995;59(3):57–60.

    Google Scholar 

  111. Seo D-H, Jeong Y-I, Kim D-G, Jang M-J, Jang M-K, Nah J-W. Methotrexate-incorporated polymeric nanoparticles of methoxy poly (ethylene glycol)-grafted chitosan. Colloids Surf B Biointerfaces. 2009;69(2):157–63.

    Article  CAS  PubMed  Google Scholar 

  112. Dwibhashyam V, Nagappa A. Strategies for enhanced drug delivery to the central nervous system. Indian J Pharm Sci. 2008;70(2):145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Blasi P, Giovagnoli S, Schoubben A, Ricci M, Rossi C. Solid lipid nanoparticles for targeted brain drug delivery. Adv Drug Deliv Rev. 2007;59(6):454–77.

    Article  CAS  PubMed  Google Scholar 

  114. Chirio D, Gallarate M, Peira E, Battaglia L, Muntoni E, Riganti C, Biasibetti E, Capucchio MT, Valazza A, Panciani P. Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in glioblastoma treatment. Eur J Pharm Biopharm. 2014;88(3):746–58.

    Article  CAS  PubMed  Google Scholar 

  115. Battaglia L, Gallarate M, Peira E, Chirio D, Muntoni E, Biasibetti E, Capucchio MT, Valazza A, Panciani PP, Lanotte M. Solid lipid nanoparticles for potential doxorubicin delivery in glioblastoma treatment: preliminary in vitro studies. J Pharm Sci. 2014;103(7):2157–65.

    Article  CAS  PubMed  Google Scholar 

  116. Salunkhe SS, Bhatia NM, Kawade VS, Bhatia MS. Development of lipid based nanoparticulate drug delivery systems and drug carrier complexes for delivery to brain. J Appl Pharm Sci. 2015;5:110–29.

    Article  CAS  Google Scholar 

  117. Göppert TM, Müller RH. 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. 2005;13(3):179–87.

    Article  PubMed  CAS  Google Scholar 

  118. Busquets MA, Espargaró A, Sabaté R, Estelrich J. Magnetic nanoparticles cross the blood-brain barrier: when physics rises to a challenge. Nanomaterials. 2015;5(4):2231–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Chen P-Y, Liu H-L, Hua M-Y, Yang H-W, Huang C-Y, Chu P-C, Lyu L-A, Tseng I-C, Feng L-Y, Tsai H-C. Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment. Neuro Oncol. 2010;12:1050–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Hua M-Y, Liu H-L, Yang H-W, Chen P-Y, Tsai R-Y, Huang C-Y, Tseng I-C, Lyu L-A, Ma C-C, Tang H-J. The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas. Biomaterials. 2011;32(2):516–27.

    Article  CAS  PubMed  Google Scholar 

  121. Qiao R, Jia Q, Huwel S, Xia R, Liu T, Gao F, Galla H-J, Gao M. Receptor-mediated delivery of magnetic nanoparticles across the blood–brain barrier. ACS Nano. 2012;6(4):3304–10.

    Article  CAS  PubMed  Google Scholar 

  122. Shubayev VI, Pisanic TR, Jin S. Magnetic nanoparticles for theragnostics. Adv Drug Deliv Rev. 2009;61(6):467–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Umezawa F, Eto Y. Liposome targeting to mouse brain: mannose as a recognition marker. Biochem Biophys Res Commun. 1988;153(3):1038–44.

    Article  CAS  PubMed  Google Scholar 

  124. Béduneau A, Saulnier P, Benoit J-P. Active targeting of brain tumors using nanocarriers. Biomaterials. 2007;28(33):4947–67.

    Article  PubMed  CAS  Google Scholar 

  125. Lindqvist A, Rip J, van Kregten J, Gaillard PJ, Hammarlund-Udenaes M. In vivo functional evaluation of increased brain delivery of the opioid peptide DAMGO by Glutathione-PEGylated liposomes. Pharm Res. 2016;33(1):177–85.

    Article  CAS  PubMed  Google Scholar 

  126. Chen Z-L, Huang M, Wang X-R, Fu J, Han M, Shen Y-Q, Xia Z, Gao J-Q. Transferrin-modified liposome promotes α-mangostin to penetrate the blood–brain barrier. Nanomedicine. 2016;12(2):421–30.

    Article  CAS  PubMed  Google Scholar 

  127. van Rooy I, Mastrobattista E, Storm G, Hennink WE, Schiffelers RM. Comparison of five different targeting ligands to enhance accumulation of liposomes into the brain. J Control Release. 2011;150(1):30–6.

    Article  PubMed  CAS  Google Scholar 

  128. Fréchet JM. Dendrimers and other dendritic macromolecules: from building blocks to functional assemblies in nanoscience and nanotechnology. J Polym Sci A Polym Chem. 2003;41(23):3713–25.

    Article  CAS  Google Scholar 

  129. Sarin H, Kanevsky AS, Wu H, Brimacombe KR, Fung SH, Sousa AA, Auh S, Wilson CM, Sharma K, Aronova MA. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells. J Transl Med. 2008;6(1):80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Yang H. Nanoparticle-mediated brain-specific drug delivery, imaging, and diagnosis. Pharm Res. 2010;27(9):1759–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Boyd BJ, Kaminskas LM, Karellas P, Krippner G, Lessene R, Porter CJ. Cationic poly-L-lysine dendrimers: pharmacokinetics, biodistribution, and evidence for metabolism and bioresorption after intravenous administration to rats. Mol Pharm. 2006;3(5):614–27.

    Article  CAS  PubMed  Google Scholar 

  132. Jannat FT-E. Synthesis of dendrimer molecules based on triazine. Dhaka: Bangladesh University of Engineering and Technology; 2006.

    Google Scholar 

  133. Nance E, Zhang F, Mishra MK, Zhang Z, Kambhampati SP, Kannan RM, Kannan S. Nanoscale effects in dendrimer-mediated targeting of neuroinflammation. Biomaterials. 2016;101:96–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, Terada Y, Kano M, Miyazono K, Uesaka M. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol. 2011;6(12):815–23.

    Article  CAS  PubMed  Google Scholar 

  135. Micheli M-R, Bova R, Magini A, Polidoro M, Emiliani C. Lipid-based nanocarriers for CNS-targeted drug delivery. Recent Pat CNS Drug Discov. 2012;7(1):71–86.

    Article  CAS  PubMed  Google Scholar 

  136. Das MK, Sarma A, Chakraborty T. Nano-ART and NeuroAIDS. Drug Deliv Transl Res. 2016;6:452–72.

    Article  CAS  PubMed  Google Scholar 

  137. Sonali AP, Singh RP, Rajesh CV, Singh S, Vijayakumar MR, Pandey BL, Muthu MS. Transferrin receptor-targeted vitamin E TPGS micelles for brain cancer therapy: preparation, characterization and brain distribution in rats. Drug Deliv. 2016;23(5):1788–98.

    Article  CAS  PubMed  Google Scholar 

  138. Zhang P, Hu L, Yin Q, Feng L, Li Y. Transferrin-modified c [RGDfK]-paclitaxel loaded hybrid micelle for sequential blood-brain barrier penetration and glioma targeting therapy. Mol Pharm. 2012;9(6):1590–8.

    Article  CAS  PubMed  Google Scholar 

  139. Yarris L. Nanocarriers may carry new hope for brain cancer therapy. Science Daily, November. 2015;19:2015.

    Google Scholar 

  140. Misra A, Ganesh S, Shahiwala A, Shah SP. Drug delivery to the central nervous system: a review. J Pharm Pharm Sci. 2003;6(2):252–73.

    CAS  PubMed  Google Scholar 

  141. Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem. 2013;2013:18.

    Article  CAS  Google Scholar 

  142. Gao H, Pang Z, Jiang X. Targeted delivery of nano-therapeutics for major disorders of the central nervous system. Pharm Res. 2013;30(10):2485–98.

    Article  CAS  PubMed  Google Scholar 

  143. Fischer HC, Chan WC. Nanotoxicity: the growing need for in vivo study. Curr Opin Biotechnol. 2007;18(6):565–71.

    Article  CAS  PubMed  Google Scholar 

  144. Fazil M, Md S, Haque S, Kumar M, Baboota S, Kaur Sahni J, Ali J. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci. 2012;47(1):6–15.

    Article  CAS  PubMed  Google Scholar 

  145. Costa PM, Cardoso AL, Mendonça LS, Serani A, Custódia C, Conceição M, Simões S, Moreira JN, de Almeida LP, de Lima MCP. Tumor-targeted chlorotoxin-coupled nanoparticles for nucleic acid delivery to glioblastoma cells: a promising system for glioblastoma treatment. Mol Ther Nucleic Acids. 2013;2(6):e100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Hamaguchi T, Doi T, Eguchi-Nakajima T, Kato K, Yamada Y, Shimada Y, Fuse N, Ohtsu A, S-i M, Takanashi M. Phase I study of NK012, a novel SN-38–incorporating micellar nanoparticle, in adult patients with solid tumors. Clin Cancer Res. 2010;16(20):5058–66.

    Article  CAS  PubMed  Google Scholar 

  147. Zhan C, Gu B, Xie C, Li J, Liu Y, Lu W. Cyclic RGD conjugated poly (ethylene glycol)-co-poly (lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. J Control Release. 2010;143(1):136–42.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Hyderabad (NIPER Hyderabad), Balanagar, Telangana, 500037, India

    Anil Kumar Kalvala, Priyanka Giri, Jyothirmai Kaligatla & Ashutosh Kumar

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Hyderabad (NIPER Hyderabad), Balanagar, Telangana, 500037, India

    Wahid Khan

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  1. Anil Kumar Kalvala
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  2. Priyanka Giri
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  5. Ashutosh Kumar
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Correspondence to Ashutosh Kumar .

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  1. Department of Immunology, Center for Personalized Nanomedicine, Institute of Neuro-Immune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA

    Ajeet Kaushik

  2. Department of Immunology, Center for Personalized Nanomedicine, Institute of Neuro-Immune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA

    Rahul Dev Jayant

  3. Department of Immunology, Center for Personalized Nanomedicine, Institute of Neuro-Immune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA

    Madhavan Nair

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Kalvala, A.K., Giri, P., Kaligatla, J., Khan, W., Kumar, A. (2017). CNS Drug Delivery for Diseases Eradication: An Overview. In: Kaushik, A., Jayant, R., Nair, M. (eds) Advances in Personalized Nanotherapeutics . Springer, Cham. https://doi.org/10.1007/978-3-319-63633-7_10

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