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Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier

David Lee, Tamara Minko

Pharmaceutics · 2021 · Review · CC BY

doi:10.3390/pharmaceutics13122049 (opens in a new tab)

Abstract

Treatment of neurodegenerative diseases or other central nervous system (CNS) disorders has always been a significant challenge. The nature of the blood-brain barrier (BBB) limits the penetration of therapeutic molecules to the brain after oral or parenteral administration, which, in combination with hepatic metabolism and drug elimination and inactivation during its journey in the systemic circulation, decreases the efficacy of the treatment, requires high drug doses and often induces adverse side effects. Nose-to-brain drug delivery allows the direct transport of therapeutic molecules by bypassing the BBB and increases drug concentration in the brain. The present review describes mechanisms of nose-to-brain drug delivery and discusses recent advances in this area with especial emphasis on nanotechnology-based approaches.

References 281

  1. 1.

    Alexander A., Agrawal M., Uddin A., Siddique S., Shehata A.M., Shaker M.A., Ata Ur Rahman S., Abdul M.I.M., Shaker M.A. Recent expansions of novel strategies towards the drug targeting into the brain. Int. J. Nanomed. 2019;14:5895-5909.

    Not in our library10.2147/ijn.s210876 (opens in a new tab)

  2. 2.

    Engelhardt B., Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: Function and dysfunction. Semin. Immunopathol. 2009;31:497-511.

    Not in our library10.1007/s00281-009-0177-0 (opens in a new tab)

  3. 3.

    Koutsari C., Dilworth T.J., Holt J., Elshaboury R., Rotschafer J.C., DiPiro J.T., Yee G.C., Posey L., Haines S.T., Nolin T.D., Ellingrod V. Central Nervous System Infections. Pharmacotherapy: A Pathopysiologic Approach, 11e. 2020.

    Not in our library

  4. 4.
  5. 5.
  6. 6.

    Rickards H. Depression in neurological disorders: Parkinson’s disease, multiple sclerosis, and stroke. J. Neurol. Neurosurg. Psychiatry. 2005;76:i48-i52.

    Not in our library10.1136/jnnp.2004.060426 (opens in a new tab)

  7. 7.

    Simonato M., Bennett J., Boulis N.M., Castro M.G., Fink D.J., Goins W.F., Gray S.J., Lowenstein P.R., Vandenberghe L.H., Wilson T.J., et al. Progress in gene therapy for neurological disorders. Nat. Rev. Neurol. 2013;9:277-291.

    Not in our library10.1038/nrneurol.2013.56 (opens in a new tab)

  8. 8.

    Blasi P., Giovagnoli S., Schoubben A., Ricci M., Rossi C. Solid lipid nanoparticles for targeted brain drug delivery. Adv. Drug Deliv. Rev. 2007;59:454-477.

    Not in our library10.1016/j.addr.2007.04.011 (opens in a new tab)

  9. 9.

    Daneman R., Prat A. The blood-brain barrier. Cold Spring Harb. Perspect. Biol. 2015;7:a020412.

    Not in our library10.1101/cshperspect.a020412 (opens in a new tab)

  10. 10.

    Miller D.S. Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier. Trends Pharmacol. Sci. 2010;31:246-254.

    Not in our library10.1016/j.tips.2010.03.003 (opens in a new tab)

  11. 11.

    Löscher W., Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005;2:86-98.

    Not in our library10.1602/neurorx.2.1.86 (opens in a new tab)

  12. 12.

    Pardridge W.M. The blood-brain barrier: Bottleneck in brain drug development. NeuroRx. 2005;2:3-14.

    Not in our library10.1602/neurorx.2.1.3 (opens in a new tab)

  13. 13.

    Ohtsuki S., Terasaki T. Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm. Res. 2007;24:1745-1758.

    Not in our library10.1007/s11095-007-9374-5 (opens in a new tab)

  14. 14.

    Hersh D.S., Wadajkar A.S., Roberts N., Perez J.G., Connolly N.P., Frenkel V., Winkles J.A., Woodworth G.F., Kim A.J. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier. Curr. Pharm. Des. 2016;22:1177-1193.

    Not in our library10.2174/1381612822666151221150733 (opens in a new tab)

  15. 15.

    Barar J., Rafi M.A., Pourseif M.M., Omidi Y. Blood-brain barrier transport machineries and targeted therapy of brain diseases. Bioimpacts. 2016;6:225-248.

    Not in our library10.15171/bi.2016.30 (opens in a new tab)

  16. 16.

    Goncalves R.A., De Felice F.G. The crosstalk between brain and periphery: Implications for brain health and disease. Neuropharmacology. 2021;197:108728.

    Not in our library10.1016/j.neuropharm.2021.108728 (opens in a new tab)

  17. 17.

    Cook A.M., Mieure K.D., Owen R.D., Pesaturo A.B., Hatton J. Intracerebroventricular administration of drugs. Pharmacotherapy. 2009;29:832-845.

    Not in our library10.1592/phco.29.7.832 (opens in a new tab)

  18. 18.
  19. 19.

    Nishikawa R., Iwata H., Sakata Y., Muramoto K., Matsuoka T. Safety of Gliadel Implant for Malignant Glioma: Report of Postmarketing Surveillance in Japan. Neurol. Med. Chir. 2021;61:536-548.

    Not in our library10.2176/nmc.oa.2021-0024 (opens in a new tab)

  20. 20.

    Shibahara I., Miyasaka K., Sekiguchi A., Ishiyama H., Inukai M., Yasui Y., Watanabe T., Sato S., Hide T., Kumabe T. Long-term follow-up after BCNU wafer implantation in patients with newly diagnosed glioblastoma. J. Clin. Neurosci. 2021;86:202-210.

    Not in our library10.1016/j.jocn.2021.01.037 (opens in a new tab)

  21. 21.

    Pires A., Fortuna A., Alves G., Falcão A. Intranasal drug delivery: How, why and what for? J. Pharm. Pharm. Sci. 2009;12:288-311.

    Not in our library10.18433/j3nc79 (opens in a new tab)

  22. 22.

    Tian L., Shang Y., Chen R., Bai R., Chen C., Inthavong K., Tu J. Correlation of regional deposition dosage for inhaled nanoparticles in human and rat olfactory. Part. Fibre Toxicol. 2019;16:6.

    Not in our library10.1186/s12989-019-0290-8 (opens in a new tab)

  23. 23.

    Dhuria S.V., Hanson L.R., Frey W.H. Intranasal delivery to the central nervous system: Mechanisms and experimental considerations. J. Pharm. Sci. 2010;99:1654-1673.

    Not in our library10.1002/jps.21924 (opens in a new tab)

  24. 24.

    Karakosta P., Alexopoulos A.H., Kiparissides C. Computational model of particle deposition in the nasal cavity under steady and dynamic flow. Comput Methods Biomech Biomed. Engin. 2015;18:514-526.

    Not in our library10.1080/10255842.2013.819856 (opens in a new tab)

  25. 25.

    Lochhead J.J., Thorne R.G. Intranasal delivery of biologics to the central nervous system. Adv. Drug Deliv. Rev. 2012;64:614-628.

    Not in our library10.1016/j.addr.2011.11.002 (opens in a new tab)

  26. 26.

    Kapoor M., Cloyd J.C., Siegel R.A. A review of intranasal formulations for the treatment of seizure emergencies. J. Control. Release. 2016;237:147-159.

    Not in our library10.1016/j.jconrel.2016.07.001 (opens in a new tab)

  27. 27.

    Bourganis V., Kammona O., Alexopoulos A., Kiparissides C. Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics. Eur. J. Pharm. Biopharm. 2018;128:337-362.

    Not in our library10.1016/j.ejpb.2018.05.009 (opens in a new tab)

  28. 28.
  29. 29.

    Kim S.J., Byun S.W., Lee S.S. Various tumors in the nasal vestibule. Int. J. Clin. Exp. Pathol. 2013;6:2713-2718.

    Not in our library

  30. 30.

    Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur. J. Pharm. Sci. 2000;11:1-18.

    Not in our library10.1016/s0928-0987(00)00087-7 (opens in a new tab)

  31. 31.

    Chatterjee B., Gorain B., Mohananaidu K., Sengupta P., Mandal U.K., Choudhury H. Targeted drug delivery to the brain via intranasal nanoemulsion: Available proof of concept and existing challenges. Int. J. Pharm. 2019;565:258-268.

    Not in our library10.1016/j.ijpharm.2019.05.032 (opens in a new tab)

  32. 32.

    Lindsay S.L., McCanney G.A., Willison A.G., Barnett S.C. Multi-target approaches to CNS repair: Olfactory mucosa-derived cells and heparan sulfates. Nat. Rev. Neurol. 2020;16:229-240.

    Not in our library10.1038/s41582-020-0311-0 (opens in a new tab)

  33. 33.

    Rock J.R., Randell S.H., Hogan B.L. Airway basal stem cells: A perspective on their roles in epithelial homeostasis and remodeling. Dis. Model. Mech. 2010;3:545-556.

    Not in our library10.1242/dmm.006031 (opens in a new tab)

  34. 34.

    Lillehoj E.P., Kato K., Lu W., Kim K.C. Cellular and molecular biology of airway mucins. Int. Rev. Cell Mol. Biol. 2013;303:139-202.

    Not in our library10.1016/b978-0-12-407697-6.00004-0 (opens in a new tab)

  35. 35.

    Lillehoj E.R., Kim K.C. Airway mucus: Its components and function. Arch. Pharm. Res. 2002;25:770-780.

    Not in our library10.1007/bf02976990 (opens in a new tab)

  36. 36.

    Fahy J.V., Dickey B.F. Airway mucus function and dysfunction. N. Engl. J. Med. 2010;363:2233-2247.

    Not in our library10.1056/nejmra0910061 (opens in a new tab)

  37. 37.

    Md S., Mustafa G., Baboota S., Ali J. Nanoneurotherapeutics approach intended for direct nose to brain delivery. Drug Dev. Ind. Pharm. 2015;41:1922-1934.

    Not in our library10.3109/03639045.2015.1052081 (opens in a new tab)

  38. 38.

    Stoeckelhuber M., Olzowy B., Ihler F., Matthias C., Scherer E.Q., Babaryka G., Loeffelbein D.J., Rohleder N.H., Nieberler M., Kesting M.R. Immunolocalization of antimicrobial and cytoskeletal components in the serous glands of human sinonasal mucosa. Histol. Histopathol. 2014;29:1315-1324.

    Not in our library10.14670/hh-29.1315 (opens in a new tab)

  39. 39.

    Walker H.K., Walker H.K., Hall W.D., Hurst J.W. Cranial Nerve I: The Olfactory Nerve. Clinical Methods: The History, Physical, and Laboratory Examinations. 1990.

    Not in our library

  40. 40.

    Harkema J.R., Carey S.A., Wagner J.G. The nose revisited: A brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium. Toxicol. Pathol. 2006;34:252-269.

    Not in our library10.1080/01926230600713475 (opens in a new tab)

All 281 references

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