NOSE-TO-BRAIN DRUG DELIVERY: AN UPDATE TO THE ALTERNATIVE PATH TO SUCCESSFUL TARGETED ANTI-MIGRAINE DRUGS

Authors

  • SOUVIK CHATTOPADHYAY Jakir Hossain Institute of Pharmacy, Raghunathganj, Murshidabad, India 742235
  • SUJIT DAS Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar, East Sikkim, India 737136
  • KOUSHIK NARAYAN SARMA Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar, East Sikkim, India 737136

DOI:

https://doi.org/10.22159/ijap.2021v13i2.40404

Keywords:

Drug delivery system, Brain targeting, Nasal route, Latest approaches, Migraine

Abstract

The Blood-Brain Barrier (BBB) limits transportation to the brain of possible treatment moieties. Specific stimulation of the brain through olfactory and trigeminal neural pathways by BBB has been taken into consideration for the development of a wide spectrum of brain therapeutics. The intranasal delivery path delivers the drugs through the brain, eliminating any side effects and increasing neurotherapeutics performance. Diverse drug delivery systems (DDDss) for reaching the brain via the nasal route have been researched over the past few decades. Large-scale molecular biologics, such as Deoxyribonucleic acid (DNA), gene vectors, and stem cells, can be administered intranasally, as a method for the management of a range of CNS illnesses, including stroke, Parkinson's diseases, multiple sclerosis, Migraine, Alzheimer's diseases, epilepsy, and mental disorders. New DDSs, including nanoparticles, liposomes, and polymeric micelles, have acquired potentials in the nasal mucosa and central nervous system (CNS), as effective means of concentrating the brain without toxicity. Differential nasal cavity structures posed a significant obstacle in ineffective drugs beyond the nasal valve. Pharmaceutical firms have increasingly used emerging techniques for the production of new nasal pharmaceutical drugs to overcome these obstacles. This review aims to identify the new advances in the nasal administration of brain-based DDSs for Migraines.

Downloads

Download data is not yet available.

References

Nutt DJ, Attridge J. CNS drug development in Europe–past progress and future challenges. Neurobiol Dis 2013;61:6–20.

Abbott A Schizophrenia. The drug deadlock. Nature 2010;468:158–9.

Global, Regional, and National Burden of Neurological Disorders During 1990-2015: A Systematic Analysis for the Global Burden of Disease Study; 2015.

Pires A, Fortuna A, Alves G, Falcao A. Intranasal drug delivery: how, why and what for. J Pharm Pharm Sci 2009;12:288–311.

Jain R, Nabar S, Dandekar P. Formulation and evaluation of novel micellar nanocarrier for nasal delivery of sumatriptan. Nanomedicine (Lond) 2010;5:575–87.

Singla DR, Kohrt BA, Murray LK, Anand A, Chorpita BF, Patel V. Psychological treatments for the world: lessons from low-and middle-income countries. Annu Rev Clin Psychol 2017;13:149–81.

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

Vasa DM, O’Donnell LA, Wildfong PL. Influence of dosage form, formulation, and delivery device on olfactory deposition and clearance: enhancement of nose-toCNS uptake. J Pharm Innov 2015;10:200–10.

Wu H, Hu K, Jiang X. From nose to brain: understanding transport capacity and transport rate of drugs. Expert Opin Drug Delivery 2008;5:1159–68.

Quintana DS, Guastella AJ, Westlye LT, Andreassen OA. The promise and pitfalls of intranasally administering psychopharmacological agents for the treatment of psychiatric disorders. Molecular Psychiatry Nature Publishing Group; 2016. p. 29–38.

Shingaki T, Hidalgo IJ, Furubayashi T, Sakane T, Katsumi H, Yamamoto A, et al. Nasal delivery of P-gp substrates to the brain through the nosebrain pathway. Drug Metab Pharmacokinet 2011;26:248–55.

Kamei N, Takeda Morishita M. Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides. J Controlled Release 2015;197:105–10.

Baba M, Itaka K, Kondo K, Yamasoba T, Kataoka K. Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles. J Controlled Release 2015;201:41–8.

Kanazawa T, Akiyama F, Kakizaki S, Takashima Y, Seta Y. Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles. Biomaterials 2013;34:9220–6.

Feigin VL, Nichols E, Alam T, Bannick MS, Beghi E, Blake N, et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol 2019;18:459–80.

Yu SP, Tung JK, Wei ZZ, Chen D, Berglund K, Zhong W, et al. Optochemogenetic stimulation of transplanted iPS-NPCs enhances neuronal repair and functional recovery after ischemic stroke. J Neurosci 2019;39:6571–94.

Falcone JA, Salameh TS, Yi X, Cordy BJ, Mortell WG, Kabanov AV, et al. Intranasal administration as a route for drug delivery to the brain: evidence for a unique pathway for albumin. J Pharmacol Exp Ther 2014;351:54–60.

Illum L. Nasal drug delivery: new developments and strategies. Drug Discovery Today 2002;7:1184–9.

Jiang Y, Li Y, Liu X. Intranasal delivery: circumventing the iron curtain to treat neurological disorders. Expert Opin Drug Delivery 2015;12:1717–25.

Panda N, Reddy AV, Subba Reddy GV, Panda KC. Formulation design and in vitro evaluation of Zolmitriptan immediate release tablets using primojel and AC-Di-Sol. J Pharm Sci Res 2015;7:545–53.

Rapoport AM, Bigal ME, Tepper SJ, Sheftell FD. Intranasal medications for the treatment of migraine and cluster headache. CNS Drugs. CNS Drugs; 2004. p. 671–85.

Wolf DA, Hanson LR, Aronovich EL, Nan Z, Low WC, Frey WH, et al. Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration. Mol Genet Metab 2012;106:131–4.

Thorne RG, Hanson LR, Ross TM, Tung D, Frey WH. Delivery of interferon-β to the monkey nervous system following intranasal administration. Neuroscience 2008;152:785–97.

Rapoport A, Winner P. Nasal delivery of antimigraine drugs: clinical rationale and evidence base. Vol. 46. Headache. Headache; 2006.

Dahlof CG, Linde M, Kerekes E. Zolmitriptan nasal spray provides fast relief of migraine symptoms and is preferred by patients: a swedish study of preference in clinical practice. J Headache Pain 2004;5:237–42.

Khan S, Patil K, Bobade N, Yeole P, Gaikwad R. Formulation of intranasal mucoadhesive temperature-mediated in situ gel containing ropinirole and evaluation of brain targeting efficiency in rats. J Drug Target 2010;18:223–34.

Ying W. The nose may help the brain: Intranasal drug delivery for treating neurological diseases. Vol. 3. Future Neurology. Future Medicine Ltd London, UK; 2008. p. 1–4.

Jadhav K, Gambhire M, Shaikh I, Kadam V, Pisal S. Nasal drug delivery system-factors affecting and applications. Curr Drug Ther 2007;2:27–38.

Shah B, Khunt D, Bhatt H, Misra M, Padh H. Intranasal delivery of venlafaxine loaded nanostructured lipid carrier: Risk assessment and QbD based optimization. J Drug Delivery Sci Technol 2016;33:37–50.

Kumar M, Misra A, Babbar AK, Mishra AK, Mishra P, Pathak K. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. Int J Pharm 2008;358:285-91.

Wang F, Jiang X, Lu W. Profiles of methotrexate in blood and CSF following intranasal and intravenous administration to rats. Int J Pharm 2003;263:1–7.

Zhang Q, Jiang X, Jiang W, Lu W, Su L, Shi Z. Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain. Int J Pharm 2004;275:85–96.

Shadab MD, Khan RA, Mustafa G, Chuttani K, Baboota S, Sahni JK, et al. Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. Eur J Pharm Sci 2013;48:393–405.

Sakane T, Akizuki M, Yamashita S, Nadai T, Hashida M, Sezaki H. The transport of a drug to the cerebrospinal fluid directly from the nasal cavity: the relation to the lipophilicity of the drug. Chem Pharm Bull 1991;39:2456–8.

Illum L. Nasal drug delivery-recent developments and future prospects. J Controlled Release 2012;161:254-63.

Wu H, Hu K, Jiang X. From nose to brain: understanding transport capacity and transport rate of drugs. Expert Opinion Drug Delivery 2008;5:1159–68.

Horvat S, Feher A, Wolburg H, Sipos P, Veszelka S, Toth A, et al. Sodium hyaluronate as a mucoadhesive component in nasal formulation enhances delivery of molecules to brain tissue. Eur J Pharm Biopharm 2009;72:252–9.

Rassu G, Soddu E, Cossu M, Brundu A, Cerri G, Marchetti N, et al. Solid microparticles based on chitosan or methyl-β-cyclodextrin: a first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate. J Controlled Release 2015;201:68–77.

Casettari L, Illum L. Chitosan in nasal delivery systems for therapeutic drugs. J Controlled Release 2014;190:189-200.

Dimova S, Brewster ME, Noppe M, Jorissen M, Augustijns P. The use of human nasal in vitro cell systems during drug discovery and development. Toxicol Vitr 2005;19:107–22.

Wong YC, Zuo Z. Intranasal delivery-modification of drug metabolism and brain disposition. Pharm Res Springer 2010;27:1208–23.

Dhamankar V, Donovan MD. Modulating nasal mucosal permeation using metabolic saturation and enzyme inhibition techniques. J Pharm Pharmacol 2017;69:1075–83.

Hussain MA, Shenvi AB, Rowe SM, Shefter E. The use of α-aminoboronic acid derivatives to stabilize peptide drugs during their intranasal absorption. Pharm Res 1989;6:186–9.

Graff CL, Pollack GM. P-glycoprotein attenuates brain uptake of substrates after nasal instillation. Pharm Res 2003;20:1225–30.

Graff CL, Pollack GM. Nasal drug administration: potential for targeted central nervous system delivery. J Pharm Sci 2005;94:1187-95.

Graff CL, Pollack GM. Functional evidence for P-glycoprotein at the nose-brain barrier. Pharm Res 2005;22:86–93.

Hada N, Netzer WJ, Belhassan F, Wennogle LP, Gizurarson S. Nose-to-brain transport of imatinib mesylate: a pharmacokinetic evaluation. Eur J Pharm Sci 2017;102:46–54.

Marttin E, Schipper NGM, Coos Verhoef J, Merkus FWHM. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Delivery Rev 1998;29:13–38.

Horvat S, Feher A, Wolburg H, Sipos P, Veszelka S, Toth A, et al. Sodium hyaluronate as a mucoadhesive component in nasal formulation enhances delivery of molecules to brain tissue. Eur J Pharm Biopharm 20091;72:252–9.

Marttin E, Verhoef JC, Merklus FWHM. Efficacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein drugs. J Drug Targeting. Harwood Academic Publishers GmbH 1998;6:17–36.

Jansson B, Hagerstrom H, Fransen N, Edsman K, Bjork E. The influence of gellan gum on the transfer of fluorescein dextran across rat nasal epithelium in vivo. Eur J Pharm Biopharm 2005;59:557–64.

Mura P, Mennini N, Nativi C, Richichi B. In situ mucoadhesive-thermosensitive liposomal gel as a novel vehicle for nasal extended delivery of opiorphin. Eur J Pharm Biopharm 2018;122:54–61.

Charlton ST, Davis SS, Illum L. Evaluation of effect of ephedrine on the transport of drugs from the nasal cavity to the systemic circulation and the central nervous system. J Drug Target 2007;15:370–7.

Mercke U, Hybbinette JC, Lindberg S. Parasympathetic and sympathetic influences on mucociliary activity in vivo. Rhinology 1982;20:201–4.

Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Jarvinen T, et al. Prodrugs: design and clinical applications. Nat Rev Drug Discovery 2008;7:255–70.

Hussain AA, Dittert LW, Qaisi AM, Traboulsi A. Method for enhancement of, Google delivery of T by the administration of its prodrugs via the nasal route. Patents. Hussain AA, Dittert LW, Qaisi AM, Traboulsi A. Method for enhancement of delivery of THC by the administration of its prodrugs via the nasal route. Google Patents 2009. p. 2.

Kao HD, Traboulsi A, Itoh S, Dittert L, Hussain A. Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs. Pharm Res 2000;17:978–84.

Gao X, Wu B, Zhang Q, Chen J, Zhu J, Zhang W, et al. Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Controlled Release 2007;121:156–67.

Soddu E, Rassu G, Giunchedi P, Sarmento B, Gavini E. From naturally-occurring neurotoxic agents to CNS shuttles for drug delivery. Eur J Pharm Sci 2015;74:63–76.

Mistry A, Stolnik S, Illum L. Nose-to-brain delivery: investigation of the transport of nanoparticles with different surface characteristics and sizes in excised porcine olfactory epithelium. Mol Pharm 2015;12:2755–66.

Gao X, Tao W, Lu W, Zhang Q, Zhang Y, Jiang X, et al. Lectin-conjugated PEG-PLA nanoparticles: Preparation and brain delivery after intranasal administration. Biomaterials 2006;27:3482–90.

Gao H. Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharmaceutica Sinica B 2016;6:268–86.

Shi NQ, Qi XR, Xiang B, Zhang Y. A survey on “trojan Horse” peptides: Opportunities, issues and controlled entry to “troy.” J Controlled Release 2014;6:53–70.

Kamei N, Shingaki T, Kanayama Y, Tanaka M, Zochi R, Hasegawa K, et al. Visualization and quantitative assessment of the brain distribution of insulin through nose-to-brain delivery based on the cell-penetrating peptide noncovalent strategy. Mol Pharm 2016;13:1004–11.

Khan T, Ranjan R, Dogra Y, Pandya SM, Shafi H, Singh SK, et al. Intranasal eutectic powder of zolmitriptan with enhanced bioavailability in the rat brain. Mol Pharm 2016;13:3234–40.

Li F, Feng J, Cheng Q, Zhu W, Jin Y. Delivery of 125I-cobrotoxin after intranasal administration to the brain: a microdialysis study in freely moving rats. Int J Pharm 2007;328:161–7.

Dhuria SV, Hanson LR, Frey WH. Novel vasoconstrictor formulation to enhance intranasal targeting of neuropeptide therapeutics to the central nervous system. J Pharmacol Exp Ther 2009;328:312–20.

Xi J, Zhang Z, Si XA. Improving intranasal delivery of neurological nanomedicine to the olfactory region using magnetophoretic guidance of microsphere carriers. Int J Nanomed 2015;10:1211–22.

Chen H, Konofagou EE. The size of blood–brain barrier opening induced by focused ultrasound is dictated by the acoustic pressure. J Cereb Blood Flow Metab 2020;34:1197–204.

Chen H, Yang GZX, Getachew H, Acosta C, Sierra Sánchez C, Konofagou EE. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor. Sci Rep 2016;6:1–8.

Chen TC, Da Fonseca CO, Schönthal AH. Perillyl alcohol and its drug-conjugated derivatives as potential novel methods of treating brain metastases. Vol. 17. International Journal of Molecular Sciences. MDPI AG; 2016.

Grassin Delyle S, Buenestado A, Naline E, Faisy C, Blouquit Laye S, Couderc LJ, et al. Intranasal drug delivery: an efficient and non-invasive route for systemic administration-focus on opioids. Pharmacol Therapeutics 2012;134:366–79.

Warnken ZN, Smyth HDC, Watts AB, Weitman S, Kuhn JG, Williams RO. Formulation and device design to increase nose to brain drug delivery. J Drug Delivery Sci Technol 2016;35:213–22.

Obaidi M, Offman E, Messina J, Carothers J, Djupesland PG, Mahmoud RA. Improved pharmacokinetics of sumatriptan with breath PoweredTM nasal delivery of sumatriptan powder. Headache J Head Face Pain 2013;53:1323–33.

Schuster NM, Rapoport AM. New strategies for the treatment and prevention of primary headache disorders. Nat Rev Neurol 2016;12:635–50.

Giroux M. Introducing controlled particle dispersiontm; 2005.

Warnken ZN, Smyth HDC, Watts AB, Weitman S, Kuhn JG, Williams RO. Formulation and device design to increase nose to brain drug delivery. J Drug Delivery Sci Technol 2016;35:213-22.

Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 2012;69:29–38.

Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, et al. Intranasal insulin improves cognition and modulates β-amyloid in early AD. Neurology 2008;70:440–8.

Bhavna Md S, Ali M, Ali R, Bhatnagar A, Baboota S. Donepezil nanosuspension intended for nose to brain targeting: in vitro and in vivo safety evaluation. Int J Biol Macromol 2014;67:418–25.

Elnaggar YSR, Etman SM, Abdelmonsif DA, Abdallah OY. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in alzheimer’s disease: optimization, biological efficacy, and potential toxicity. J Pharm Sci 2015;104:3544–56.

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

Agrawal M, Saraf S, Saraf S, Antimisiaris SG, Chougule MB, Shoyele SA, et al. Nose-to-brain drug delivery: an update on clinical challenges and progress towards approval of anti-alzheimer drugs. J Controlled Release 2018;281:139-77.

Alexander A, Dwivedi S, Ajazuddin, Giri TK, Saraf S, Saraf S, et al. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. J Controlled Release 2012;164:26–40.

Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J Pharm Pharmacol 2001;53:3–22.

Dhuria SV, Hanson LR, Frey WH. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci 2010;99:1654–73.

Pires PC, Santos AO. Nanosystems in nose-to-brain drug delivery: a review of non-clinical brain targeting studies. J Controlled Release 2018;270:89–100.

Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. Mechanism of intranasal drug delivery directly to the brain. Life Sci 2018;195:45-52.

Scheibe M, Bethge C, Witt M, Hummel T. Intranasal administration of drugs. Arch Otolaryngol Head Neck Surg 2008;134:643–6.

Djupesland PG, Skretting A, Winderen M, Holand T. Breath actuated device improves delivery to target sites beyond the nasal valve. Laryngoscope 2006;116:466–72.

Van Den Berg MP, Merkus P, Romeijn SG, Verhoef JC, Merkus FWHM. Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans. J Drug Target 2003;11:325–31.

Al-Ghananeem AM, Traboulsi AA, Dittert LW, Hussain AA. Targeted brain delivery of 17β-estradiol via nasally administered water soluble prodrugs. AAPS PharmSciTech 2002;3:E5.

Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American migraine study II. Headache 2001;41:646–57.

Olesen J, Bes A, Kunkel R, Lance JW, Nappi G, Pfaffenrath V, et al. The international classification of headache disorders. 3rd edition (beta version). Cephalalgia 2013;33:629–808.

Kalam MA, Sultana Y, Ali A, Aqil M, Mishra AK, Chuttani K. Preparation, characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system. J Drug Target 2010;18:191–204.

Ahmed Kassem A. Formulation approaches of triptans for management of migraine. Curr Drug Delivery 2016;13:882–98.

Abbas Z, Marihal S, Sk A. Almotriptan loaded sodium alginate microspheres for nasal delivery: formulation optimization using factorial design, characterization and in vitro evaluation. Indian J Novel Drug Delivery 2014;6:10-24.

Oakley CB, Kossoff EH. Migraine and epilepsy in the pediatric population topical collection on childhood and adolescent headache. Curr Pain Headache Rep 2014;18:402.

Zarcone D, Corbetta S. Shared mechanisms of epilepsy, migraine and affective disorders. Neurol Sci 2017;38:73–6.

Swaminathan A, Smith JH. Migraine and vertigo. Vol. 15. Current neurology and neuroscience reports. Curr Med Group LLC 1; 2015.

Wells RE, Turner DP, Lee M, Bishop L, Strauss L. Managing migraine during pregnancy and lactation. current neurology and neuroscience reports. Curr Med Group LLC 1; 2016.

Abdou EM, Kandil SM, Miniawy HMFE. Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion. Int J Pharm 2017;529:667–77.

Abd-Elal RMA, Shamma RN, Rashed HM, Bendas ER. Trans-nasal zolmitriptan novasomes: in vitro preparation, optimization and in vivo evaluation of brain targeting efficiency. Drug Delivery 2016;23:3374–86.

Youssef NAHA, Kassem AA, Farid RM, Ismail FA, EL-Massik MAE, Boraie NA. A novel nasal almotriptan loaded solid lipid nanoparticles in mucoadhesive in situ gel formulation for brain targeting: preparation, characterization and in vivo evaluation. Int J Pharm 2018;548:609–24.

Al-Salama ZT, Scott LJ. Sumatriptan nasal powder: a review in acute treatment of migraine. Drugs 2016;76:1477–84.

Gulati N, Nagaich U, Saraf SA. Intranasal delivery of chitosan nanoparticles for migraine therapy. Sci Pharm 2013;81:843–54.

Abbas Z, Marihal S. Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: formulation optimization using factorial design, characterization, and in vitro evaluation. J Pharm Bioallied Sci 2014;6:267–77.

Silberstein S. AVP-825: a novel intranasal delivery system for low-dose sumatriptan powder in the treatment of acute migraine. Expert Rev Clin Pharmacol 2017;10:821–32.

Published

07-03-2021

How to Cite

CHATTOPADHYAY, S., DAS, S., & SARMA, K. N. (2021). NOSE-TO-BRAIN DRUG DELIVERY: AN UPDATE TO THE ALTERNATIVE PATH TO SUCCESSFUL TARGETED ANTI-MIGRAINE DRUGS. International Journal of Applied Pharmaceutics, 13(2), 67–75. https://doi.org/10.22159/ijap.2021v13i2.40404

Issue

Section

Review Article(s)