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Applications of Biotechnology in Neurology pp 477–511Cite as

Role of Biotechnology in Drug Delivery to the Nervous System

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Abstract

The delivery of drugs to the brain is a challenge in the treatment of CNS disorders (Jain 2010). The major obstruction to CNS drug delivery is the blood–brain barrier (BBB), which limits the access of drugs to the brain substance. In the past, treatment of CNS disease was done mostly with systemically administered drugs. This trend continues. Most CNS-disorder research is directed toward the discovery of drugs and formulations for controlled release; little attention has been paid to the method of delivery of these drugs to the brain. Now biotechnology is making a significant contribution to drug delivery in disorders of the CNS.

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References

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

    Article  PubMed  CAS  Google Scholar 

  • Abulrob A, Sprong H, Van Bergen en Henegouwen P, Stanimirovic D. The blood–brain barrier transmigrating single domain antibody: mechanisms of transport and antigenic epitopes in human brain endothelial cells. J Neurochem 2005; 95:1201–14.

    Google Scholar 

  • Banks WA. Developing drugs that can cross the blood–brain barrier: applications to Alzheimer’s disease. BMC Neurosci 2008; 9(Suppl 3):S2.

    Article  PubMed  Google Scholar 

  • Batson OV. The function of the vertebral veins and their role in the spread of metastases, Ann Surg 1940; 112:138–49.

    Article  PubMed  CAS  Google Scholar 

  • Begley DJ. ABC transporters and the blood–brain barrier. Curr Pharm Des 2004; 10:1295–312.

    Article  PubMed  CAS  Google Scholar 

  • Boado RJ. A new generation of neurobiological drugs engineered to overcome the challenges of brain drug delivery. Drug News Perspect 2008; 21:489–503.

    Article  PubMed  CAS  Google Scholar 

  • Broman T. The possibilities of the passage of substances from the blood to the central nervous system. Acta Psych Neurol 1941; 16:1–25.

    Article  CAS  Google Scholar 

  • Chua JY, Pendharkar AV, Wang N, et al. Intra-arterial injection of neural stem cells using a microneedle technique does not cause microembolic strokes. J Cereb Blood Flow Metab 2011; 31:1263–71.

    Article  PubMed  Google Scholar 

  • Cooper IS. Intracerebral injection of procaine into the globus pallidus in hyperkinetic disorders. Science 1954; 119:417–8.

    Article  PubMed  CAS  Google Scholar 

  • Corning JL. Spinal anesthesia and local medication of the cord. NY Med J 1885; 42:483–5.

    Google Scholar 

  • Cucullo L, Hossain M, Puvenna V, Marchi N, Janigro D. The role of shear stress in blood–brain barrier endothelial physiology. BMC Neuroscience 2011; 12:40.

    Article  PubMed  CAS  Google Scholar 

  • Ding H, Inoue S, Ljubimov AV, et al. Inhibition of brain tumor growth by intravenous poly(β-Lmalic acid) nanobioconjugate with pH-dependent drug release. PNAS 2010; 107:18143–8.

    Article  PubMed  CAS  Google Scholar 

  • Doppman JL. Intra-arterial valium--its safety and effectiveness. Radiology 1973; 106:335–8.

    PubMed  CAS  Google Scholar 

  • Ehrlich P. “Das sauerstoffbedürfnis des organismus,” eine farbanalytische studie. Berlin: Hirschwald, 1885.

    Google Scholar 

  • Emerich DF, Thanos CG. In vitro culture duration does not impact the ability of encapsulated choroid plexus transplants to prevent neurological deficits in an excitotoxin-lesioned rat model of Huntington’s disease. Cell Transplant 2006; 15:595–602.

    Article  PubMed  Google Scholar 

  • Enerson BE, Drewes LR. The rat blood–brain barrier transcriptome. J Cereb Blood Flow Metab 2006; 26:959–73.

    Article  PubMed  CAS  Google Scholar 

  • Eyal S, Ke B, Muzi M, et al. Regional P-glycoprotein activity and inhibition at the human blood–brain barrier as imaged by positron emission tomography. Clin Pharmacol Ther 2010; 87:579–85.

    Article  PubMed  CAS  Google Scholar 

  • Fischer UM, Harting MT, Jimenez F, et al. Pulmonary Passage is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect. Stem Cells and Development 2009; 18:683–92.

    Article  PubMed  CAS  Google Scholar 

  • Gaillard PJ, Appeldoorn CC, Rip J, et al. Enhanced brain delivery of liposomal methylprednisolone improved therapeutic efficacy in a model of neuroinflammation. J Control Release 2012 Jun 23. [Epub ahead of print].

    Google Scholar 

  • Gaillard PJ, de Boer AG. 2B-Trans-Technology: targeted delivery across the blood–brain barrier. In, Jain KK (ed) Drug Delivery Systems, Springer/Humana Press, 2008:161–175.

    Google Scholar 

  • Gaillard PJ. Case Study: to-BBB’s G-Technology®, getting the best from drug-delivery research with industry-academia partnerships. Therapeutic Delivery 2011; 2:1391–94.

    Article  PubMed  Google Scholar 

  • Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in PD. Nat Med 2003; 9:589–95.

    Article  PubMed  CAS  Google Scholar 

  • Gimi B, Leong T, Gu Z, et al. Self-assembled 3D radiofrequency-shielded (RS) containers for cell encapsulation. Biomedical Microdevices 2005; 7:341–5.

    Article  PubMed  Google Scholar 

  • Glantz MJ, Van Horn A, Fisher R, Chamberlain MC. Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis. Cancer 2010; 116:1947–52.

    Article  PubMed  Google Scholar 

  • Goldmann E. Vitalfarbungen am Zentralnervensystem. Beitrag zur Physio-Pathologie des Plexus Choroideus und der Hirnhaute (Intravital labeling of the central nervous system. A study on the pathophysiology of the choroid plexus and the meninges). Abhandlungen der konigliche preussischen Akademie der Wissenshaften, Physikalisch-Mathematische Klasse 1913; 1:1–64.

    Google Scholar 

  • Gynther M, Laine K, Ropponen J, et al. Large neutral amino acid transporter enables brain drug delivery via prodrugs. J Med Chem 2008; 51:932–6.

    Article  PubMed  CAS  Google Scholar 

  • Hu J, Yuan X, Ko MK, et al. Calcium-activated potassium channels mediated blood–brain tumor barrier opening in a rat metastatic brain tumor model. Mol Cancer 2007;6:22.

    Article  PubMed  Google Scholar 

  • Jain KK. Nanobiotechnology-based strategies for crossing the blood–brain barrier. Nanomedicine 2012; 7:1225–33.

    Article  PubMed  CAS  Google Scholar 

  • Jain KK. Drug delivery to the central nervous system. Basel, Switzerland: Jain PharmaBiotech Publications, 2012a.

    Google Scholar 

  • Jain KK. An overview of drug delivery to the central nervous system. Neuromethods 2010; 45:1–13.

    Article  CAS  Google Scholar 

  • Johansson I, Ingelman-Sundberg M. Genetic polymorphism and toxicology--with emphasis on cytochrome p450. Toxicol Sci 2011; 120:1–13.

    Article  PubMed  CAS  Google Scholar 

  • Karkan D, Pfeifer C, Vitalis TZ, et al. A Unique Carrier for Delivery of Therapeutic Compounds beyond the Blood–brain Barrier. PLoS ONE 2008; 3:e2469.

    Article  PubMed  Google Scholar 

  • Kramer K, Humm JL, Souweidane MM, et al. Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. J Clin Oncol 2007; 25:5465–70.

    Article  PubMed  Google Scholar 

  • Kreuter J, Gelperina S. Use of nanoparticles for cerebral cancer. Tumori 2008; 94:271–7.

    PubMed  CAS  Google Scholar 

  • Kwan P, Brodie MJ. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia 2005; 46:224–35.

    Article  PubMed  CAS  Google Scholar 

  • Lanevskij K, Japertas P, Didziapetris R, Petrauskas A. Prediction of blood–brain barrier penetration by drugs. In: Jain KK, editor. Drug Delivery to the Central Nervous System. New York: Humana/Springer, 2010:63–83.

    Chapter  Google Scholar 

  • Latour LL, Kang DW, Ezzeddine MA, et al. Early blood–brain barrier disruption in human focal brain ischemia. Ann Neurol 2004; 56:468–77.

    Article  PubMed  Google Scholar 

  • Lazorthes Y, Sallerin-Caute B, Verdie JC, Bastide R. Advances in drug delivery systems and applications in neurosurgery. Adv Tech Stand Neurosurg 1991; 18:143–92.

    Article  PubMed  CAS  Google Scholar 

  • LeBowitz JH. A breach in the blood–brain barrier. Proc Natl Acad Sci USA 2005; 102:14485–6.

    Article  PubMed  CAS  Google Scholar 

  • Lewandowski M. Zur Lehre der Cerebrospinalflüssigkeit. Z Klin Med 1900; 40:480–94.

    Google Scholar 

  • Miller DS, Bauer B, Hartz AM. Modulation of P-glycoprotein at the blood–brain barrier: opportunities to improve central nervous system pharmacotherapy. Pharmacol Rev 2008; 60:196–209.

    Article  PubMed  CAS  Google Scholar 

  • Misra V, Lal A, El Khoury R, et al. Intra-Arterial Delivery of Cell Therapies for Stroke. Stem Cells Dev 2012; 21:1007–15.

    Article  PubMed  CAS  Google Scholar 

  • Namanja HA, Emmert D, Pires MM, et al. Inhibition of human P-glycoprotein transport and substrate binding using a galantamine dimer. Biochem Biophys Res Commun 2009; 388:672–6.

    Article  PubMed  CAS  Google Scholar 

  • Pan W, Kastin AJ, Zankel TC, et al. Efficient transfer of RAP across the blood–brain barrier. J Cell Sci 2004; 117:5071–78.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM. Re-engineering biopharmaceuticals for delivery to brain with molecular Trojan horses. Bioconjug Chem 2008; 19:1327–38.

    Article  PubMed  CAS  Google Scholar 

  • Prince WS, McCormick LM, Wendt DJ, et al. Lipoprotein receptor binding, cellular uptake, and lysosomal delivery of fusions between the receptor-associated protein (RAP) and alpha-L-iduronidase or acid alpha-glucosidase. J Biol Chem 2004; 279:35037–46.

    Article  PubMed  CAS  Google Scholar 

  • Reese TS, Karnovsky MJ. Fine structural localization of a blood–brain barrier to exogenous peroxidase. J Cell Biol 1967; 34:207–17.

    Article  PubMed  CAS  Google Scholar 

  • Sarkar D, Spencer JA, Phillips JA, et al. Engineered cell homing. Blood 2011; 118:e184–91.

    Article  PubMed  CAS  Google Scholar 

  • Shawahna R, Uchida Y, Decleves X, et al. Transcriptomic and Quantitative Proteomic Analysis of Transporters and Drug Metabolizing Enzymes in Freshly Isolated Human Brain Microvessels. Mol Pharm 2011; 8:1332–41.

    Article  PubMed  CAS  Google Scholar 

  • Shen F, Li AA, Gong YK, et al. Encapsulation of Recombinant Cells with a Novel Magnetized Alginate for Magnetic Resonance Imaging. Human Gene Therapy 2005; 16:971–84.

    Article  PubMed  CAS  Google Scholar 

  • Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, Young B. Improvement of bilateral motor functions in patients with PD through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg 2005; 102:216–22.

    Article  PubMed  CAS  Google Scholar 

  • Spiegel EA, Wycis HA, Marks M, Lee AJ. Stereoscopic apparatus for operations on the human brain. Science 1947; 106:349–50.

    Article  PubMed  CAS  Google Scholar 

  • Stern L, Gautier R. Les rapports entre le liquide céphalo-rachidien et al. circulation sanguine. Arch Int Physiol 1922; 17:391–448.

    Article  Google Scholar 

  • Stern L, Gautier R. Rapports entre le liquide céphalo-rachidien et al. circulation sanguine. Arch Int Physiol 1921; 17:138–92.

    Article  CAS  Google Scholar 

  • Suresh Reddy J, Venkateswarlu V, Koning GA. Radioprotective effect of transferrin targeted citicoline liposomes. J Drug Target 2006; 14:13–9.

    Article  PubMed  Google Scholar 

  • Tatard VM, Venier-Julienne MC, Saulnier P, et al. Pharmacologically active microcarriers: a tool for cell therapy. Biomaterials 2005; 26:3727–37.

    Article  PubMed  CAS  Google Scholar 

  • Veiseh O, Sun C, Fang C, et al. Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood–brain barrier. Cancer Res 2009; 69:6200–7.

    Article  PubMed  CAS  Google Scholar 

  • Weiler-Guttler H, Zinke H, Mockel B, Frey A, Gassen HG. cDNA cloning and sequence analysis of the glucose transporter from porcine blood–brain barrier. Biol Chem Hoppe Seyler 1989; 370:467–73.

    Article  PubMed  CAS  Google Scholar 

  • Wilson B, Samanta MK, Santhi K, Kumar KP, Paramakrishnan N, Suresh B. Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer’s disease. Brain Res 2008; 1200:159–68.

    Article  PubMed  CAS  Google Scholar 

  • Wong HL, Chattopadhyay N, Wu XY, Bendayan R. Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Adv Drug Deliv Rev 2010; 62:503–17.

    Article  PubMed  CAS  Google Scholar 

  • Zheng PP, Romme E, van der Spek PJ, Dirven CM, Willemsen R, Kros JM. Glut1/SLC2A1 is crucial for the development of the blood–brain barrier in vivo. Ann Neurol 2010; 68:835–44.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Jain PharmaBiotech, Basel, Switzerland

    Kewal K. Jain MD, FRACS, FFPM

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  1. Kewal K. Jain MD, FRACS, FFPM
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Jain, K.K. (2013). Role of Biotechnology in Drug Delivery to the Nervous System. In: Applications of Biotechnology in Neurology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-272-8_13

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