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A Review: Nose to Brain Drug Delivery for Various CNS Disorders

  • Sachin Jadhav
  • Sabuj Sahoo
  • Sagar Kumar Mishra
Conference paper

Abstract

Currently the nasal route has been utilized for local delivery of drugs for treating nasal allergy, congestion, and infections. However, the use of a nasal route for systemic drug delivery has begun for drugs requiring rapid onset of action or need to avoid first pass effect through the oral route. The diseases of CNS like epilepsy, migraine, Alzheimer’s etc. desires direct drug delivery to the brain for the treatment and nasal drug delivery system exhibited promising results for some of such CNS diseases and disorders. Various dosage forms for nasal drug delivery have been formulated and evaluated by various researchers like nasal sprays, nasal pumps, nasal gels, solutions, suspensions, micro emulsions, mucoadhesive gels, mucoadhesive microspheres, and dry powder formulations.

Keywords

Drug delivery CNS diseases Nose to the brain 

References

  1. 1.
    Dekker M (2002) Encyclopedia of pharmaceutical technology. Informa, New YorkGoogle Scholar
  2. 2.
    Pires A, Fortuna A, Alves G, Falcao A (2009) Intranasal drug delivery: how, why and what for? J Pharm Sci 12(3):288–311Google Scholar
  3. 3.
    Mistry A, Stolnik S, Illum L (2009) Nanoparticle for direct nose to brain delivery of drugs. Int J Pharm 379:146–157CrossRefGoogle Scholar
  4. 4.
    Arorra P, Sharma S, Garry S (2002) Permeability issues in nasal drug delivery. Drug Discov Today 7:967–975CrossRefGoogle Scholar
  5. 5.
    Kaliner M, Marin Z, Patoe C, Shelhamer J (1984) Human respiratory mucus. J Allergy Clin Immunol 73:318–323CrossRefGoogle Scholar
  6. 6.
    Pires A, Fortuna A, Alves G, Falcao A (2009) Intranasal drug delivery: how, why and what for? J Pharm Pharm Sci 12(3):288–311CrossRefGoogle Scholar
  7. 7.
    Schipper NG, Verhoef JC, Merkos AN (1991) The nasal mucocilliary clearance relevance to nasal drug delivery. Pharm Res 8:807–814CrossRefGoogle Scholar
  8. 8.
    Mygind N, Anggard A (1984) Anatomy and physiology of the nose – pathophysiological alterations in allergic rhinitis. Clin Rev Allergy 2:173–188Google Scholar
  9. 9.
    Chien YW, Chang SF (1987) Intranasal drug delivery for systemic medication. Crit Rev Ther Drug Carrier Syst 4:67–194Google Scholar
  10. 10.
    Illum L (2000) Transport of drugs from the nasal cavity to the CNS. Eur J Pharm Sci 11:1–18CrossRefGoogle Scholar
  11. 11.
    Mathison S, Nagilla R, Kompello UB (1998) Nasal route for direct delivery of solutes to the central nervous system: fact or fiction? J Drug Target 5:415–441CrossRefGoogle Scholar
  12. 12.
    Hehar SS, Mason JDT, Stephen AB, Washington N, Jones NS, Jackson SJ et al (1999) Twenty four hour ambulatory nasal pH monitoring. Clin Otolaryngol 24:24–25CrossRefGoogle Scholar
  13. 13.
    Chien YW, Su KSE, Chang S (1989) Nasal systemic drug delivery. Marcel Dekker, New York, pp 1–38Google Scholar
  14. 14.
    Stevens A, Lowe J (1997) Human histology. Mosby, PhiladelphiaGoogle Scholar
  15. 15.
    Charlton S, Jones NS, Davis SS, Illum L (2007) Distribution and clearance of bioadhesive formulations from the olfactory region in man: effect of polymer type and nasal delivery device. Eur J Pharm Sci 30:295–302CrossRefGoogle Scholar
  16. 16.
    Illum L (2004) Is nose-to-brain transport of drugs in man a reality? J Pharm Pharmacol 56:3–17CrossRefGoogle Scholar
  17. 17.
    Frey WH (2002) Drug Deliv Technol 2:46–49Google Scholar
  18. 18.
    Vyas TK, Shahiwala A, Marathe S, Mishra A (2005) Curr Drug Deliv 2:165–175Google Scholar
  19. 19.
    Thornton Manning JR, Dahl AR (1997) Metabolic capacity of nasal tissue interspecies comparison of xenobiotics – metabolising enzymes. Mutat Res 380:43–59CrossRefGoogle Scholar
  20. 20.
    Lewis JL, Nikula KJ, Novak R, Dahl AR (1994) Comparative localisation of carboxylesterase in F344 rat, beagle dog and human nasal tissue. Anat Rec 239:55–64CrossRefGoogle Scholar
  21. 21.
    Aceto A, Llio CD, Argeluccis, Longo V, Gervasi PG, Federici G (1989) Glutathione transferases inhuman nasal mucosa. Arch Toxicol 63:427–431CrossRefGoogle Scholar
  22. 22.
    Thorne RG, Prank GJ, Padmanabhan V (2004) Neurosciences 127:481–496CrossRefGoogle Scholar
  23. 23.
    Thorne RG, Frey WH (2001) Delivery of neurotrophic factors to the CNS: pharmacokinetic consideration. Clin Pharmacol 40:907–946CrossRefGoogle Scholar
  24. 24.
    Thorne RG, Elmary CR, Ala TA, Frey WH 2nd (1995) Quantitative analysis of the olfactory pathway for drug delivery to brain. Brain Res 692:278–282CrossRefGoogle Scholar
  25. 25.
    Balin BJ, Broadwell RD, Salcman M, el-kalling M (1986) Avenues for entry of peripherally administered protein to the CNS in mouse, rat, squirrel and monkey. J Comp Neurol 251:260–280CrossRefGoogle Scholar
  26. 26.
    Broadwell RD, Balin BJ (1985) Endocytic and exocytic pathway of the neuronal secretory process and trans synaptic transfer of wheat germ agglutinin- horseradish peroxidase in vivo. J Comp Neurol 242:632–650CrossRefGoogle Scholar
  27. 27.
    Frey WH, Liu J, Thorne RG, Rahman YE (1995) Intranasal delivery of 125I labelled nerve growth factor to the brain via the olfactory route. In: Inqbal K, Monimor JA, Winblad B, Wisniewski HM (eds) Research advances in Alzheimer’s disease and related disorders. Wiley, New York, pp 329–335Google Scholar
  28. 28.
    Frey WH, Liu J, Chen X, Thorne RG, Fawcelts JR, Alg TA (1997) Delivery of 125I-NGF to brain via olfactory route. Drug Deliv 4:87–92CrossRefGoogle Scholar
  29. 29.
    Chen XQ, Fawcelt JR, Rahman YE, Ala TA, Frey WH (1998) Delivery of nerve growth factor to the brain via the olfactory pathway. J Alzheimers Dis 1:35–44CrossRefGoogle Scholar
  30. 30.
    Frey WH, Thorne RG, Prank G (2000) Delivery of insulin like growth factor to the brain and spinalcord along olfactory and trigeminal pathway following Intranasal administration: a noninvasive method for bypassing the blood brain barrier. Soc Neurosci 26:1365–1370Google Scholar
  31. 31.
    Born J, Lang T, Kern W et al (2002) Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 5:514–516CrossRefGoogle Scholar
  32. 32.
    Sakane T, Akizuki M, Yamashita S et al (1994) Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the dissociation of the drug. J Pharm Pharmacol 46:378–379CrossRefGoogle Scholar
  33. 33.
    Yang JP, Linb HJ, Chenga SM, Wang ZL, Cheng X, Yuck HX, Lina XF (2009) Neurosci Lett 449:108–111Google Scholar
  34. 34.
    Ross TM, Martinez PM, Renner JC, Thorne RG, Hanson LR, Frey WH (2004) J Neuroimmunol 151:66–77Google Scholar
  35. 35.
    Oldi MF (1996) Lymphology 29:1–9Google Scholar
  36. 36.
    Pardrige WM (2007) Blood brain barrier delivery. Drug Discov Today 12(1/2):54–61CrossRefGoogle Scholar
  37. 37.
    Pardeshi CV, Belgamwar VS (2013) Direct nose to brain drug delivery via integrated nerve Pathways bypassing the blood-brain barrier: an excellent platform for brain targeting. Expert Opin Drug Deliv 10(7):957–972CrossRefGoogle Scholar
  38. 38.
    Zia H, Dordeti D, Needham TF (1993) Intranasal drug delivery. Clin Res Regul Aff 10:99–135CrossRefGoogle Scholar
  39. 39.
    Hussain AA, AI-Bayatti AA, Dakkuri A, Okochi K, Hussain MA (2002) Testosterne 17beta-N,N-dimethyl glycerinate hydrochloride: a prodrug with potential for nasal delivery of testosterone. J Pharm Sci 28(3):785–789CrossRefGoogle Scholar
  40. 40.
    Illum L, Watts P, Fisher AN, Hinchliffe M, Norbury H, Gill J, Nankervis R, Davis SS (2002) Intranasal delivery of morphine. J Pharmacol Exp Ther 16(8):391–340CrossRefGoogle Scholar
  41. 41.
    Morimoto K, Miyazaki M, Kakemi M (1995) Effects of proteolytic enzyme inhibitors on nasal absorption of salmon calcitonin in rats. Int J Pharm 113:1–8CrossRefGoogle Scholar
  42. 42.
    Greimel A, Bernko P, schnurch A, Delcurto MD, D’Antonio M (2007) Transport characterisation of beta sheet breaker peptide across excised bovine nasal mucosa. Drug Dev Ind Pharm 33:71–77CrossRefGoogle Scholar
  43. 43.
    Higuchi T, Stella V (1975) Prodrug as novel drug delivery systems. American Chemical Society, Washington, DCCrossRefGoogle Scholar
  44. 44.
    Martin E, Nicolaas GM, Schipp J, Coos V, Frons WH (1997) Nasal mucocilliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev 29:13–38CrossRefGoogle Scholar
  45. 45.
    Kao HD, Traboulsi A, Itoh S, Dittert L, Hussain A (2000) Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs. Pharm Res 17:978–984CrossRefGoogle Scholar
  46. 46.
    Hussain AA, Al-Bayatti AA, Dakkuri A, Okochi K, Hussain MA (2002) Testesterone 17β-N,N-dimethylglycinate hydrochloride: a prodrug with a potential for nasal delivery of testesterone. J Pharm Sci 91:785–789CrossRefGoogle Scholar
  47. 47.
    Yang C, Gao H, Mitra AK (2001) Chemical stability, enzymatic hydrolysis and nasal uptake of amino acid ester prodrugs of acyclovir. J Pharm Sci 90:617–624CrossRefGoogle Scholar
  48. 48.
    Ugwoke MI, Agu RU, Verbeke N, Kinget R (2005) Nasal mucoadhesive drug delivery background, applications, trends and future perspectives. Adv Drug Deliv Rev 57:1640–1665CrossRefGoogle Scholar
  49. 49.
    Ramprasad YV et al (1996) Intranasal drug delivery systems: overview. Indian J Pharm Sci 58:1–8Google Scholar
  50. 50.
    O’Hagan DT, Illum L (1990) Absorption of peptides and proteins from the respiratory tract and the potential for development of locally administered vaccine. Crit Rev Ther Drug Carrier Syst 7(1):35–97Google Scholar
  51. 51.
    Durrani Z, McInterney TL, Mclain L et al (1998) Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1- specific IgA and IgG than oral immunization. J Immunol Methods 220:93–103CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Sachin Jadhav
    • 1
  • Sabuj Sahoo
    • 1
  • Sagar Kumar Mishra
    • 1
  1. 1.University Department of Pharmaceutical SciencesUtkal UniversityBhubaneshwarIndia

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