Please note this is a comparison between Version 2 by Vivi Li and Version 1 by Sonia Trombino.
Recently, the intranasal route has emerged as a promising administration site for central nervous system therapeutics since it provides a direct connection to the central nervous system, avoiding the passage through the blood–brain barrier, consequently increasing drug cerebral bioavailability.
stimuli-responsive hydrogel
intranasal administration
nose to brain
neurodegenerative diseases
Alzheimer’s disease
Parkinson’s disease
drug delivery
Please wait, diff process is still running!
References
Feigin, V.L.; Nichols, E.; Alam, T.; Bannick, M.S.; Beghi, E.; Blake, N.; Culpepper, W.J.; Dorsey, E.R.; Elbaz, A.; Ellenbogen, R.G.; 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, 459–480.
Feigin, V.L.; Vos, T.; Nichols, E.; Owolabi, M.O.; Carroll, W.M.; Dichgans, M.; Deuschl, G.; Parmar, P.; Brainin, M.; Murray, C. The global burden of neurological disorders: Translating evidence into policy. Lancet Neurol. 2020, 19, 255–265.
Carroll, W.M. The global burden of neurological disorders. Lancet Neurol. 2019, 18, 418–419.
Neurological Disorders, Public Health Challenges. Available online: (accessed on 31 December 2006.).
Simonato, M.; Bennett, J.; Boulis, N.M.; Castro, M.G.; Fink, D.J.; Goins, W.F.; Glorioso, J.C. Progress in gene therapy for neurological disorders. Nat. Rev. Neurol. 2013, 9, 277–291.
Kanwar, J.R.; Sriramoju, B.; Kanwar, R.K. Neurological disorders and therapeutics targeted to surmount the blood–brain barrier. Int. J. Nanomed. 2012, 7, 3259–3278.
Agrawal, M.; Saraf, S.; Saraf, S.; Dubey, S.K.; Puri, A.; Gupta, U.; Alexander, A. Stimu-li-responsive In situ gelling system for nose-to-brain drug delivery. J. Control. Release 2020, 327, 235–265.
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.
Aderibigbe, B.A. In situ-based gels for nose to brain delivery for the treatment of neurological dis-eases. Pharmaceutics 2018, 10, 40.
Kozlovskaya, L.; Abou-Kaoud, M.; Stepensky, D. Quantitative analysis of drug delivery to the brain via nasal route. J. Control. Release 2014, 189, 133–140.
Pandit, R.; Chen, L.; Götz, J. The blood-brain barrier: Physiology and strategies for drug delivery. Adv. Drug Deliv. Rev. 2020, 165, 1–14.
Obermeier, B.; Daneman, R.; Ransohoff, R.M. Development, maintenance and disruption of the blood-brain barrier. Nat. Med. 2013, 19, 1584–1596.
Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte–endothelial interactions at the blood–brain bar-rier. Nat. Rev. Neurosci. 2006, 7, 41.
Banks, W.A. From blood–brain barrier to blood–brain interface: New opportunities for CNS drug de-livery. Nat. Rev. Drug Discov. 2016, 15, 275.
Banks, A.W. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol. 2009, 9, 3.
Pardridge, W.M. The blood-brain barrier: Bottleneck in brain drug development. NeuroRx 2005, 2, 3–14.
Mittal, D.; Ali, A.; Shadab; Baboota, S.; Sahni, J.K.; Ali, J. Insights into direct nose to brain delivery: Current status and future perspective. Drug Deliv. 2013, 21, 75–86.
Pardeshi, C.V.; Belgamwar, V.S. 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. 2013, 10, 957–972.
Erdő, F.; Bors, L.A.; Farkas, D.; Bajza, Á.; Gizurarson, S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res. Bull. 2018, 143, 155–170.
Grassin-Delyle, S.; Buenestado, A.; Naline, E.; Faisy, C.; Blouquit-Laye, S.; Couderc, L.J.; Devillier, P. Intranasal drug delivery: An efficient and non-invasive route for systemic administration: Focus on opioids. Pharmachol. Ther. 2012, 134, 366–379.
Gizurarson, S. Anatomical and Histological Factors Affecting Intranasal Drug and Vaccine Delivery. Curr. Drug Deliv. 2012, 9, 566–582.
Gänger, S.; Schindowski, K. Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa. Pharmaceutics 2018, 10, 116.
Crowe, T.P.; Greenlee, M.H.W.; Kanthasamy, A.G.; Hsu, W.H. Mechanism of intranasal drug de-livery directly to the brain. Life Sci. 2018, 195, 44–52.
Watelet, J.B.; Cauwenberge, P.V. Applied anatomy and physiology of the nose and paranasal si-nuses. Allergy 1999, 54, 14–25.
Ugwoke, I.M.; Agu, R.U.; Verbeke, N.; Kinget, R. Nasal mucoadhesive drug delivery: Background, applications, trends and future perspectives. Adv. Drug Deliv. Rev. 2005, 57, 1640–1665.
Lochhead, J.J.; Thorne, R.G. Intranasal delivery of biologics to the central nervous system. Adv. Drug Deliv. Rev. 2012, 64, 614–628.
Arora, P.; Sharma, S.; Garg, S. Permeability issues in nasal drug delivery. Drug Discov. Today 2002, 7, 967–975.
Illum, L. Transport of drugs from the nasal cavity to the central nervous system. Eur. J. Pharm. Sci. 2000, 11, 1–18.
Veronesi, M.C.; Alhamami, M.; Miedema, S.B.; Yun, Y.; Ruiz-Cardozo, M.; Vannier, M.W. Imaging of intranasal drug delivery to the brain. Am. J. Nucl. Med. Mol. Imaging. 2020, 10, 1–31.
Dhuria, S.V.; Hanson, L.R.; Frey II, W.H. Intranasal delivery to the central nervous system: Mechanisms and experimental considerations. J. Pharm. Sci. 2010, 99, 1654–1673.
Balin, B.J.; Broadwell, R.D.; Salcman, M.; El-Kalliny, M. Avenues for entry of peripherally admin-istered protein to the central nervous system in mouse, rat, and squirrel monkey. J. Comp. Neurol. 1986, 251, 260–280.
Altner, H.; Altner-Kolnberger, I. Freeze-fracture and tracer experiments on the permeability of the zonulae occludentes in the olfactory mucosa of vertebrates. Cell Tissue Res. 1974, 154, 51–59.
Keller, L.A.; Merkel, O.; Popp, A. Intranasal drug delivery: Opportunities and toxicologic challenges during drug development. Drug Deliv. Transl. Res. 2021, 1, 1–23.
Thorne, R.G.; Pronk, G.J.; Padmanabhan, V.; Frey Ii, W.H. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administra-tion. Neuroscience 2004, 127, 481–496.
Thorne, R.G.; Frey, W.H. Delivery of neurotrophic factors to the central nervous system. Clin. Pharmacokinet. 2001, 40, 907–946.
Luzzati, V.; Benoit, E.; Charpentier, G.; Vachette, P. X-ray Scattering Study of Pike Olfactory Nerve: Elastic, Thermodynamic and Physiological Properties of the Axonal Membrane. J. Mol. Biol. 2004, 343, 199–212.
Van Riel, D.; Leijten, L.M.; Verdijk, R.M.; Kessel, G.C.; van der Vries, E.; van Rossum, A.M.; Kuiken, T. Evidence for influenza virus CNS invasion along the olfactory route in an immunocom-promised infant. J. Infect. Dis. 2014, 210, 419–423.
Kristensson, K.; Olsson, Y. Uptake of exogenous proteins in mouse olfactory cells. Acta Neuropathol. 1971, 19, 145–154.
Broadwell, R.D.; Balin, B.J. Endocytic and exocytic pathways of the neuronal secretory process and trans synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo. J. Comp. Neurol. 1985, 242, 632–650.
De Lorenzo, A.D. The olfactory neuron and the blood-brain barrier. In Ciba Foundation Symposium-Internal Secretions of the Pancreas (Colloquia on Endocrinology); John Wiley Sons, Ltd.: Chichester, UK, 1970; pp. 151–176.
Haberly, L.B.; Price, J.L. The axonal projection patterns of the mitral and tufted cells of the olfac-tory bulb in the rat. Brain Res. 1977, 129, 152–157.
Illum, L. Is nose-to-brain transport of drugs in man a reality? J. Pharm. Pharm. 2010, 56, 3–17.
Nonaka, N.; Farr, S.A.; Kageyama, H.; Shioda, S.; Banks, W.A. Delivery of Galanin-Like Peptide to the Brain: Targeting with Intranasal Delivery and Cyclodextrins. J. Pharm. Exp. 2008, 325, 513–519.
Charlton, S.T.; Whetstone, J.; Fayinka, S.T.; Read, K.D.; Illum, L.; Davis, S.S. Evaluation of Direct Transport Pathways of Glycine Receptor Antagonists and an Angiotensin Antagonist from the Nasal Cavity to the Central Nervous System in the Rat Model. Pharm. Res. 2008, 25, 1531–1543.
Clerico, D.; To, W.; Lanza, D. Anatomy of the Human Nasal Passages. In Handbook of Olfaction and Gustation; Apple Academic Press: Palm Bay, FL, USA, 2003; pp. 1–16.
Schaefer, M.L.; Bottger, B.; Silver, W.L.; Finger, T.E. Trigeminal collaterals in the nasal epithelium and olfactory bulb: A potential route for direct modulation of olfactory information by trigeminal stimuli. J. Comp. Neurol. 2002, 444, 221–226.
Johnson, N.J.; Hanson, L.R.; Frey, I.W.H. Trigeminal Pathways Deliver a Low Molecular Weight Drug from the Nose to the Brain and Orofacial Structures. Mol. Pharm. 2010, 7, 884–893.
Thorne, R.G.; Hanson, L.R.; Ross, T.M.; Tung, D.; Frey, W.H., II. Delivery of interferon-beta to the monkey nervous system following intranasal administration. Neuroscience 2008, 152, 785–797.
Hallschmid, M. Intranasal Insulin for Alzheimer’s Disease. CNS Drugs 2021, 35, 21–37.
Yang, J.-P.; Liu, H.-J.; Cheng, S.-M.; Wang, Z.-L.; Cheng, X.; Yu, H.-X.; Liu, X.-F. Direct transport of VEGF from the nasal cavity to brain. Neurosci. Lett. 2009, 449, 108–111.
Kanazawa, T.; Kaneko, M.; Niide, T.; Akiyama, F.; Kakizaki, S.; Ibaraki, H.; Seta, Y. Enhancement of nose-to-brain delivery of hydrophilic macromolecules with stearate-or polyethylene glycol-modified argi-nine-rich peptide. Int. J. Pharm. 2017, 530, 195–200.
Chung, E.P.; Cotter, J.D.; Prakapenka, A.V.; Cook, R.L.; DiPerna, D.M.; Sirianni, R.W. Targeting small molecule delivery to the brain and spinal cord via intranasal administration of rabies virus glycopro-tein (RVG29)-modified PLGA nanoparticles. Pharmaceutics 2020, 12, 93.
Hoffman, A.S. Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 2012, 64, 18–23.
Trombino, S.; Servidio, C.; Curcio, F.; Cassano, R. Strategies for hyaluronic acid-based hydrogel de-sign in drug delivery. Pharmaceutics 2019, 11, 407.
Karavasili, C.; Fatouros, D.G. Smart materials: In situ gel-forming systems for nasal delivery. Drug Discov. Today 2016, 21, 157–166.
Singh, R.M.; Kumar, A.; Pathak, K. Mucoadhesive in situ nasal gelling drug delivery systems for modulated drug delivery. Expert Opin. Drug Deliv. 2013, 10, 115–130.
Narayanaswamy, R.; Torchilin, V.P. Hydrogels and Their Applications in Targeted Drug Delivery. Molecules 2019, 24, 603.
Giuliano, E.; Paolino, D.; Fresta, M.; Cosco, D. Mucosal applications of poloxamer 407-based hy-drogels: An overview. Pharmaceutics 2018, 10, 159.
Abdeltawab, H.; Svirskis, D.; Sharma, M. Formulation strategies to modulate drug release from poloxamer based in situ gelling systems. Expert Opin. Drug Deliv. 2020, 17, 495–509.
Balakrishnan, P.; Park, E.-K.; Song, C.-K.; Ko, H.-J.; Hahn, T.-W.; Song, K.-W.; Cho, H.-J. Carbopol-Incorporated Thermoreversible Gel for Intranasal Drug Delivery. Molecules 2015, 20, 4124–4135.
Ur-Rehman, T.; Tavelin, S.; Gröbner, G. Chitosan in situ gelation for improved drug loading and retention in poloxamer 407 gels. Int. J. Pharm. 2011, 409, 19–29.
Ahmed, S.; Gull, A.; Aqil, M.; Ansari, M.D.; Sultana, Y. Poloxamer-407 thickened lipid colloidal system of agomelatine for brain targeting: Characterization, brain pharmacokinetic study and behavioral study on Wistar rats. Colloids Surf. B Biointerfaces 2019, 181, 426–436.
Wang, Q.; Zuo, Z.; Cheung, C.K.C.; Leung, S.S.Y. Updates on thermosensitive hydrogel for nasal, ocular and cutaneous delivery. Int. J. Pharm. 2019, 559, 86–101.
Long, J.M.; Holtzman, D.M. Alzheimer disease: An update on pathobiology and treatment strate-gies. Cell 2019, 179, 312–339.
Van der Kant, R.; Goldstein, L.S.; Ossenkoppele, R. Amyloid-β-independent regulators of tau pa-thology in Alzheimer disease. Nat. Rev. Neurosci. 2020, 21, 21–35.
Leng, F.; Edison, P. Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here? Nat. Rev. Neurol. 2021, 17, 157–172.
Abouhussein, D.M.; Khattab, A.; Bayoumi, N.A.; Mahmoud, A.F.; Sakr, T.M. Brain targeted ri-vastigmine mucoadhesive thermosensitive in situ gel: Optimization, in vitro evaluation, radiolabeling, in vivo pharmacokinetics and biodistribution. J. Drug Deliv. Sci. Technol. 2018, 43, 129–140.
Zhang, L.; Yang, S.; Wong, L.R.; Xie, H.; Ho, P.C.-L. In Vitro and In Vivo Comparison of Curcumin-Encapsulated Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles and Curcumin/Hydroxypropyl-β-Cyclodextrin Inclusion Complexes Administered Intranasally as Therapeutic Strategies for Alzheimer’s Disease. Mol. Pharm. 2020, 17, 4256–4269.
Vingtdeux, V.; Dreses-Werringloer, U.; Zhao, H.; Davies, P.; Marambaud, P. Therapeutic potential of resveratrol in Alzheimer’s disease. BMC Neurosci. 2008, 9, 1–5.
Son, I.H.; Park, Y.H.; Lee, S.I.; Yang, H.D.; Moon, H.-I. Neuroprotective Activity of Triterpenoid Saponins from Platycodi radix Against Glutamate-induced Toxicity in Primary Cultured Rat Cortical Cells. Molecules 2007, 12, 1147–1152.
Chen, W.; Li, R.; Zhu, S.; Ma, J.; Pang, L.; Ma, B.; Du, L.; Jin, Y. Nasal timosaponin BII dually sensitive in situ hydrogels for the prevention of Alzheimer’s disease induced by lipopolysaccharides. Int. J. Pharm. 2020, 578, 119115.
Armstrong, M.J.; Okun, M.S. Diagnosis and treatment of Parkinson disease: A review. JAMA 2020, 323, 548–560.
Armstrong, M.J.; Okun, M.S. Choosing a Parkinson Disease Treatment. JAMA 2020, 323, 1420.
Pfeiffer, R. Gastrointestinal Dysfunction in Parkinson’s Disease. Parkinson’s Dis. 2004, 2, 107–116.
Guay, D.R. Rasagiline (TVP-1012): A new selective monoamine oxidase inhibitor for Parkinson’s disease. Am. J. Geriatr. Pharmacother. 2006, 4, 330–346.
Ravi, P.R.; Aditya, N.; Patil, S.; Cherian, L. Nasal in-situ gels for delivery of rasagiline mesylate: Improvement in bioavailability and brain localization. Drug Deliv. 2015, 22, 903–910.
Waters, C. The Development of the Rotigotine Transdermal Patch: A Historical Perspective. Neurol. Clin. 2013, 31, S37–S50.
Wang, F.; Yang, Z.; Liu, M.; Tao, Y.; Li, Z.; Wu, Z.; Gui, S. Facile nose-to-brain delivery of rotigo-tine-loaded polymer micelles thermosensitive hydrogels: In vitro characterization and in vivo behavior study. Int. J. Pharm. 2020, 577, 119046.
Kok, R.M.; Reynolds, C.F. Management of depression in older adults: A review. JAMA 2017, 317, 2114–2122.
Verduijn, J.; Milaneschi, Y.; Schoevers, R.A.; Van Hemert, A.M.; Beekman, A.T.F.; Penninx, B.W.J.H. Pathophysiology of major depressive disorder: Mechanisms involved in etiology are not associated with clinical progression. Transl. Psychiatry 2015, 5, e649.
Kupfer, D.J. The pharmacological management of depression. Dialog Clin. Neurosci. 2005, 7, 191–205.
Clevenger, S.S.; Malhotra, D.; Dang, J.; VanLe, B.; Ishak, W.W. The role of selective serotonin reuptake inhibitors in preventing relapse of major depressive disorder. Adv. Psychopharmacol. 2018, 8, 49–58.
Thakkar, H.; Vaghela, D.; Patel, B.P. Brain targeted intranasal in-situ gelling spray of paroxe-tine: Formulation, characterization and in-vivo evaluation. J. Drug Deliv. Sci. Technol. 2021, 62, 102317.
Bhandwalkar, M.J.; Avachat, A.M. Thermoreversible nasal in situ gel of venlafaxine hydro-chloride: Formulation, characterization, and pharmacodynamic evaluation. AAPS Pharmscitech 2013, 14, 101–110.
Marder, S.R.; Cannon, T.D. Schizophrenia. N. Engl. J. Med. 2019, 381, 1753–1761.
Majcher, M.J.; Babar, A.; Lofts, A.; Leung, A.; Li, X.; Abu-Hijleh, F.; Hoare, T. In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the in-tranasal delivery of an antipsychotic peptide. J. Control. Release 2021, 330, 738–752.
Kuriakose, D.; Xiao, Z. Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives. Int. J. Mol. Sci. 2020, 21, 7609.
Xie, H.; Li, L.; Sun, Y.; Wang, Y.; Gao, S.; Tian, Y.; Ma, X.; Guo, C.; Bo, F.; Zhang, L. An Available Strategy for Nasal Brain Transport of Nanocomposite Based on PAMAM Dendrimers via In Situ Gel. Nanomaterials 2019, 9, 147.