Abstract
A major barrier to entry of neuropeptides into the brain is low bioavailability and presence of the blood–brain barrier. Intranasal delivery of neuropeptides provides a potentially promising alternative to other routes of administration, since a direct pathway exists between the olfactory neuroepithelium and the brain. Use of the rat as an animal model in nose to brain delivery of neuropeptides allows for several advantages, including a large surface area within the nasal cavity dedicated to olfactory epithelium and robust neuronal pathways extending to and from most areas of the brain from the nose via the olfactory cortex. A major disadvantage to using rats for nose to brain delivery is the difficulty in selectively targeting the posterior olfactory epithelium (which facilitates delivery to the brain) over the more anterior respiratory epithelium (which facilitates delivery to the lungs and secondarily to the peripheral blood) in the nasal cavity. We have developed a novel delivery system that consists of surgically implanting stainless-steel cannulas in the dorsal aspect of the nasal cavity overlying the olfactory neuroepithelium, thereby allowing neuropeptide compounds to bypass the respiratory epithelium.
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References
Chow, H.S., Chen, Z., and Matsuura, G.T. (1999) Direct transport of cocaine from the nasal cavity to the brain following intranasal cocaine administration in rats. J. Pharm. Sci. 88, 754–758.
Hussain, A.A. (1998) Intranasal drug delivery. Adv. Drug Deliv. Rev. 29, 39–49.
Sakane, T., Akizuki, M., Taki, Y., Yamashita, S., Sezaki H., and Nadai, T. (1995) Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the molecular weight of drugs. J. Pharm. Pharmacol. 47, 379–381.
Sakane, T., Akizuki, M., Yamashita, S., Sezaki, H., Nadai, T. (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, 378–379.
Sakane, T., Akizuki, M., Yoshida, M., Yamashita, S., Nadai, T., et al. (1991) Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity. J. Pharm. Pharmacol. 43, 449–451.
Agarwal, V., and Mishra, B. (1999) Recent trends in drug delivery systems: intranasal drug delivery. Indian J. Exp. Biol. 37, 6–16.
Lewis, J.L., and Dahl A.R. (1995) Ofactory mucosa: composition, enzymatic localization, and metabolism. In: Handbook of olfaction and gustation ed. RL Doty, pp. 33–52. New York: Marcel Dekker, Inc.
Kubek, M., Yard, M., Lahiri, D.K., and Domb, A.J. (2007) Characterization of Novel Intranasal Sustained-Release Nanoparticles for Delivery of Neuropeptides to the Brain. In Nanoparticles for pharmaceutical applications, ed. TY Domb A, Ravi Kumar NV, pp. 73–84. New York: American Scientific Publishers.
Kubek, M.J., Domb, A.J., and Veronesi, M.C. (2009) Attenuation of kindled seizures by intranasal delivery of neuropeptide-loaded nanoparticles. Neurotherapeutics 6, 359–371.
Egleton, R.D., and Davis, T.P. (2005) Development of neuropeptide drugs that cross the blood-brain barrier. NeuroRx 2, 44–53.
Hökfelt, T., Broberger, C., Xu, Z.Q., Sergeyev, V., Ubink, R., and Diez, M. (2000) Neuropeptides--an overview. NeuropharmacoÂlogy 39, 1337–1356.
Strand, F.L. (2005) The neuropeptide concept and the evolution of neuropeptides In Neuropeptides: Regulators of Physiological Processes, ed. FL Strand, pp. 3–18. Cambridge: MIT Press.
Liu, X.F., Fawcett, J.R., Thorne, R.G., DeFor, T.A., and Frey, W.H, 2nd. (2001) Intranasal administration of insulin-like growth factor-I bypasses the blood-brain barrier and protects against focal cerebral ischemic damage. J. Neurol. Sci. 187, 91–97.
Semkova, I., and Krieglstein, J. (1999) Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain Res. Brain Res. Rev. 30, 176–188.
Bjorbaek, C., and Kahn, B.B. (2004) Leptin signaling in the central nervous system and the periphery. Recent Prog. Horm. Res. 59, 305–331.
Gale, S.M., Castracane, V.D., and Mantzoros, C.S. (2004) Energy homeostasis, obesity and eating disorders: recent advances in endocrinology. J. Nutr. 134, 295–298.
Gentilucci, L. (2004) New trends in the development of opioid peptide analogues as advanced remedies for pain relief. Curr. Top. Med. Chem. 4, 19–38.
Lim, K.C., Lim, S.T., and Federoff, H.J. (2003) Neurotrophin secretory pathways and synaptic plasticity. Neurobiol. Aging 24, 1135–1145.
Claes, S.J. (2004) Corticotropin-releasing hormone (CRH) in psychiatry: from stress to psychopathology. Ann. Med. 36, 50–61.
Datar, P., Srivastava, S., Coutinho, E., and Govil G. (2004) Substance P: structure, function, and therapeutics. Curr. Top. Med. Chem. 4, 75–103.
Strohle, A., and Holsboer, F. (2003) Stress responsive neurohormones in depression and anxiety. Pharmacopsychiatry 36, S207–214.
Balasubramaniam, A. (2002) Clinical potentials of neuropeptide Y family of hormones. Am. J. Surg. 183, 430–434.
Binaschi, A., Bregola, G., and Simonato, M. (2003) On the role of somatostatin in seizure control: clues from the hippocampus. Rev. Neurosci. 14, 285–301.
Kubek, M.J., and Garg, B.P. (2002) Thyrotropin-releasing hormone in the treatment of intractable epilepsy. Pediatr. Neurol. 26, 9–17.
Veronesi, M.C., Aldouby, Y., Domb, A.J., and Kubek, M.J. (2009) Thyrotropin-releasing hormone d,l polylactide nanoparticles (TRH-NPs) protect against glutamate toxicity in vitro and kindling development in vivo. Brain Res. 1303, 151–160.
Purves, D., Augustine, G.J., Fitzpatrick, D., Hall, W.C., LaMantia, A.-S., McNamara, J.O., and White, L. (2008) Neuroscience. Sunderland, MA. Sinauer Assoc.
Gizurarson, S. (1990). Animal models for intranasal drug delivery studies. A review article. Acta Pharm. Nord. 2, 105–122.
De Rosa, R., Garcia, A.A., Braschi, C., Capsoni, S., Maffei L, et al. (2005) Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice. Proc. Natl. Acad. Sci. USA 102, 3811–3816.
Frey, W. (2002) Intranasal delivery: bypassing the blood brain barrier to deliver therapeutic agents to the brain and spinal cord. Drug Deliv. Technol. 151, 66–77.
Ross, T.M., Martinez, P.M., Renner, J.C., Thorne, R.G., Hanson, L.R., and Frey, W.H., 2nd. (2004) Intranasal administration of interferon beta bypasses the blood-brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis. J. Neuroimmunol. 151, 66–77.
Thorne, R.G., and Frey, W.H., 2nd. (2001) Delivery of neurotrophic factors to the central nervous system: pharmacokinetic considerations. Clin. Pharmacokinet. 40, 907–946.
Thorne, R.G., Pronk, G.J., Padmanabhan, V., and Frey, W.H., 2nd. (2004) Delivery of insulin-like growth factor-I to the rat brain and Âspinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 127, 481–496.
Alcalay, R.N., Giladi, E., Pick, C.G., and Gozes, I. (2004) Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety-like behavior in aging mice in the elevated plus maze. Neurosci Lett. 361, 128–131.
Gozes, I., Giladi, E., Pinhasov, A., Bardea, A., and Brenneman, D.E. (2000) Activity-dependent neurotrophic factor: intranasal administration of femtomolar-acting peptides improve performance in a water maze. J. Pharmacol. Exp. Ther. 293, 1091–1098.
Born, J., Lange, T., Kern, W., McGregor, G.P., Bickel, U., and Fehm, H.L. (2002) Sniffing neuropeptides: a transnasal approach to the human brain. Nat. Neurosci. 5, 514–516.
Capsoni, S., Giannotta, S., and Cattaneo, A. (2002) Nerve growth factor and galantamine ameliorate early signs of neurodegeneration in anti-nerve growth factor mice. Proc. Natl. Acad. Sci. USA 99, 12432–12437.
Chen, X.Q., Fawcett, J.R., Rahman, Y.E., Ala, T.A., and Frey, I.W. (1998) Delivery of nerve growth factor to the brain via the olfactory pathway. J. Alzheimers. Dis. 1, 35–44.
Gozes, I., Bardea, A., Reshef, A., Zamostiano, R., Zhukovsky, S. et al. (1996) Neuroprotective strategy for Alzheimer disease: intranasal administration of a fatty neuropeptide. Proc. Natl. Acad. Sci. USA 93, 427–432.
Illum, L. (1996) Nasal delivery. The use of animal models to predict performance in man. J. Drug Target 3, 427–442.
Vaccarezza, O.L., Sepich, L.N., and Tramezzani, J.H. (1981) The vomeronasal organ of the rat. J. Anat. 132, 167–185.
Gao, X., Tao, W., Lu, W., Zhang, Q., Zhang, Y. et al. 2006. Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration. Biomaterials 27, 3482–3490.
Veronesi, M.C., Kubek, D.J., and Kubek M.J. (2007) Intranasal delivery of a thyrotropin-releasing hormone analog attenuates seizures in the amygdala-kindled rat. Epilepsia 48, 2280–2286.
Meredith, M. (2001) Human vomeronasal organ function: A critical review of best and worst cases. Chem. Senses 26, 433–445.
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Veronesi, M.C., Kubek, D.J., Kubek, M.J. (2011). Intranasal Delivery of Neuropeptides. In: Merighi, A. (eds) Neuropeptides. Methods in Molecular Biology, vol 789. Humana Press. https://doi.org/10.1007/978-1-61779-310-3_20
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DOI: https://doi.org/10.1007/978-1-61779-310-3_20
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