Vía intranasal: una alternativa para la administración de fármacos de acción central en equinos

Administración intranasal de fármacos

  • María Inés Velloso Facultad de Ciencias Veterinarias. Universidad Nacional de La Plata.
  • Violeta Ferreira Facultad de Ciencias Veterinarias. Universidad Nacional de La Plata.
  • Mariangeles Vita Facultad de Ciencias Veterinarias. Universidad Nacional de La Plata.
  • María Fabiana Landoni Facultad de Ciencias Veterinarias. Universidad Nacional de La Plata.
Palabras clave: Via Intranasal, fármacos de acción central, pasaje nariz-cerebro, equinos


La vía intranasal es reconocida en medicina humana como una vía muy promisoria para la administración sistémica y cerebral de fármacos. Es una vía de administración indolora, incruenta, económica y práctica. Por sus características, es muy útil para la aplicación de fármacos en pacientes con alteraciones orales, con diarrea o que no cooperen. Además, es una potencial vía directa al sistema nervioso central (SNC). Su uso en medicina veterinaria es muy raro, salvo para la administración de tratamientos locales. En la especie equina, aun cuando no hay estudios completos y profundos sobre las características anatomofisiológicas de la cavidad nasal, su gran superficie e irrigación (área potencial de absorción) permiten inferir su viabilidad para la administración sistémica de fármacos. En el presente artículo se discuten las características de la cavidad nasal de los equinos en relación a las diversas vías de absorción sistémica y del transporte nariz-cerebro
de fármacos, así como las potenciales aplicaciones de esta vía de administración.


La descarga de datos todavía no está disponible.


Cargando métricas ...


Agarwal V, Mishra B. 1999. Recent trends in drug delivery systems: intranasal drug delivery. Indian Journal of Experimental Biology. 37(1):6-16.

Alpar HO, Eyles JE, Williamson ED, Somavarapu S. 2001. Intranasal vaccination against plague, tetanus and diphtheria. Advanced Drug Delivery Reviews. 51(1-3):173-201.

Baker H, Spencer RF. 1986. Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Experimental Brain Research. 63:461-73. doi: 10.1007/BF00237470.

Balin BJ, Broadwell RD, Salcman M, el-Kalliny M. 1986. Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. The Journal of Comparative Neurology. 251(2):260-80. doi: 10.1002/cne.902510209.

Banks WA, During MJ, Niehoff ML. 2004. Brain uptake of the glucagon-like peptide-1 antagonist exendin(9-39) after intranasal administration. Journal of Pharmacology and Experimental Therapeutics. 309 (2):469-75. doi:10.1124/jpet.103.063222.

Benedict C, Frey WH 2nd, Schiöth, HB, Schultes B, Born J, Hallschmid M. 2011. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments. Experimental Gerontology. 46(2-3):112-5. doi: 10.1016/j.exger.2010.08.026.

Boulton M, Flessner M, Armstrong D, Mohamed R, Hay J, Johnston M. 1999. Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the rat. American Journal of Physiology. 276(3):R818–R23. doi:10.1152/ajpregu.1999.276.3.R818.

Bourganis V, Kammona O, Alexopoulos A, Kiparissides C. 2018. Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics. European Journal of Pharmaceutics and Biopharmaceutics. 128:337-62. doi:10.1016/j.ejpb.2018.05.009.

Bradbury MW, Cserr HF, Westrop RJ. 1981. Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit. American Journal of Physiology. 240(4):F329–F36. doi: 10.1152/ajprenal.1981.240.4.F329.

Broadwell RD, Balin BJ. 1985. Endocytic and exocytic pathways of the neuronal secretory process and trans synaptic transfer of wheat germ agglutinin‐horseradish peroxidase in vivo. The Journal of Comparative Neurology. 242(4):632-50. doi: 10.1002/cne.902420410.

Buck LB. 2000. The chemical senses. En: Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science. 4th edition. New York, McGraw-Hill Companies. pp. 625-52.

Cauna N. 1982. Blood and nerve supply of the nasal lining. En: Proctor DF, Andersen I, editors. The nose: Upper airway physiology and the atmospheric environment. Amsterdam: Elsevier Biomedical Press. pp. 45–69.

Charlton ST, Whetstone J, Fayinka ST, Read KD, Illum L, Davis SS. 2008. 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. Pharmaceutical Research. 25(7):1531-43. doi: 10.1007/s11095-008-9550-2.

Clerico DM, To WC, Lanza DC. 2003. Anatomy of the human nasal passages. En: Doty RL, editor. Handbook of olfaction and gustation. 2nd edition. New York: Marcel Dekker. Inc. pp. 1-16.

Corbo DC, Huang YC, Chien, YW. 1989. Nasal delivery of progestational steroids in ovariectomized rabbits. II. Effect of penetrant hydrophilicity. International Journal of Pharmaceutics. 50(3):253-60. doi: 10.1016/0378-5173(89)90128-2.

Cserr HF, Harling-Berg CJ, Knopf PM. 1992. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathology. 2 (4):269-76. doi.org/10.1111/j.1750-3639.1992.tb00703.x.

Dando SJ, Mackay-Sim A, Norton R, Currie BJ, St John JAS, Ekberg, JA, Batzloff M, Ulett GC, Beacham IR. 2014. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clinical Microbiology Reviews. 27(4): 691-726. doi: 10.1128/CMR.00118-13.

DeSesso JM. 1993. The relevance to humans of animal models for inhalation studies of cancer in the nose and upper airways. Qual Assur. 2(3):213-31.

Dhanda DS, Frey WH 2nd, Leopold D, Kompella UB. 2005. Approaches for drug deposition in the human olfactory epithelium. Journal of Drug Delivery Science and Technology. 5:64-72.

Dhuria SV, Hanson LR, Frey WH 2nd. 2009. Novel vasoconstrictor formulation to enhance intranasal targeting of neuropeptide therapeutics to the central nervous system. Journal of Pharmacology and Experimental Therapeutics. 328(1):312-20. doi: 10.1124/jpet.108.145565.

Dhuria SV, Hanson LR, Frey WH 2nd. 2010. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. Journal of Pharmaceutical Sciences. 99(4):1654-73. doi: 10.1002/jps.21924.

Einer-Jensen N, Hunter RHF. 2005. Counter-current transfer in reproductive biology. Society for Reproduction and Fertility. 129(1):9-18. doi: 10.1530/rep.1.00278.

Falcone JA, Salameh, TS, Yi X, Cordy BJ, Mortell WG, Kabanov AV, Banks WA. 2014. Intranasal administration as a route for drug delivery to the brain: Evidence for a unique pathway for albumin. Journal of Pharmacology and Experimental Therapeutics. 351(1):54-60. doi: 10.1124/jpet.114.216705.

Ferreira V, Teme Centurion O, Monina M, Landoni, MF. 2015. Evaluación de la vía intranasal para la administración de opioides en equinos. V Jornadas de Jóvenes Investigadores "Ciencia y Sociedad". Buenos Aires. Invet 17(1):63.

Ferreira V, Zapata G, Landoni MF. 2018. Disposición plasmática del butorfanol tras su administración intranasal e intravenosa en equinos. VIII Jornadas de Jóvenes Investigadores. Buenos Aires. Invet 20(1):120.

Fisher AN, Brown K, Davis SS, Parr GD, Smith DA. 1987. The effect of molecular size on the nasal absorption of water‐soluble compounds in the albino rat. Journal of Pharmacy and Pharmacology. 39(5):357-62. doi: 10.1111/j.2042-7158.1987.tb03398.x.

Frey WH II. 1991. InWPTO, editor. Neurologic agents for nasal administration to the brain. US: Chiron Corporation.

Frey WH II. 2002. Bypassing the blood-brain barrier to delivery therapeutic agents to the brain and spinal cord. Journal of Drug Delivery Science and Technology. 2:46-9. doi: 10.1186/1471-2202-9-S3-S5.

Gänger S, Schindowski K. 2018. Tailoring formulations for intranasal nose-to-brain delivery: a review on architecture, physicochemical characteristics and mucociliary clearance of the nasal olfactory mucosa. Pharmaceutics. 10(3):116-44. doi: 10.3390/pharmaceutics10030116.

Grassin-Delyle S, Buenestado A, Naline, E, Faisy C, Blouquit-Laye S, Couderc LJ, Le Guen M, Fischler M, Devillier P. 2012. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacology & Therapeutics. 134(3):366-79. doi: 10.1016/j.pharmthera.2012.03.003.

Gray H. 1978. Gray’s anatomy. 15th revised edition (Classic Collectors edition). New York, Bounty Books.

Grevers G, Herrmann U. 1987. Fenestrated endothelia in vessels of the nasal mucosa. An electron-microscopic study in the rabbit. Archives of Otorhinolaryngology. 244(1):55-60.

Groothuis DR, Vavra MW, Schlageter KE, Kang EW, Itskovich AC, Hertzler S, Allen CV, Lipton HL. 2007. Efflux of drugs and solutes from brain: The interactive roles of diffusional transcapillary transport, bulk flow and capillary transporters. Journal of Cerebral Blood Flow and Metabolism. 27(1):43-56. doi.org/10.1038/sj.jcbfm.9600315.

Hadaczek P, Yamashita Y, Mirek H, Tamas L, Bohn MC, Noble C, Park JW, Bankiewicz K. 2006. The ‘‘perivascular pump’’ driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain. Molecular Therapy. 14(1):69-78. doi: 10.1016/j.ymthe.2006.02.018.

Hanson LR, Frey WH 2nd. 2008. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neuroscience. 9:S5. doi: 10.1186/1471-2202-9-S3-S5.

Hare WCD. 1982. Capítulo 19: Sistema respiratorio de los equinos. En: Getty R, Sisson S, Grossman JD. Anatomía de los animales domésticos. Tomo I. 5ta edición. Barcelona, Salvat Editores S.A, pp. 557-72.

Hashizume R, Ozawa T, Gryaznov SM, Bollen AW, Lamborn KR, Frey WH 2nd, Deen DF. 2008. New therapeutic approach for brain tumors: Intranasal delivery of telomerase inhibitor GRN163. Neuro-Oncology. 10(2):112-20. doi: 10.1215/15228517-2007-052.

Hedin L, Olsson B, Diczfalusy M, Flyg C, Petersson AS, Rosberg S, Albertsson-Wikland K. 1993. Intranasal administration of human growth hormone (hGH) in combination with a membrane permeation enhancer in patients with GH deficiency: a pharmacokinetic study. The Journal of Clinical Endocrinology & Metabolism. 76(4): 962-7. doi:10.1210/jcem.76.4.8473411.

Jansson B, Bjork E. 2002. Visualization of in vivo olfactory uptake and transfer using fluorescein dextran. Journal of Drug Targeting. 10(5):379-86 doi:10.1080/1061186021000001823.

Jones D, Woolfson AD, Brown AF. 1997. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers. International Journal of Pharmaceutics. 151(2):223-33. doi.org/10.1016/S0378-5173(97)04904-1.

Kida S, Pantazis A, Weller RO. 1993. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathology and Applied Neurobiology. 19(6):480-8. doi.org/10.1111/j.1365-2990.1993.tb00476.x.

Kristensson K, Olsson Y. 1971. Uptake of exogenous proteins in mouse olfactory cells. Acta Neuropathologica. 19(2):145-54.

Kublik H, Vidgren MT. 1998. Nasal delivery systems and their effect on deposition and absorption. Advanced Drug Delivery Reviews. 29(1-2):157-77. doi.org/10.1016/S0169-409X(97)00067-7.

Lee VH, Yamamoto A. 1989. Penetration and enzymatic barriers to peptide and protein absorption. Advanced Drug Delivery Reviews. 4(2):171-207. doi: 10.1016/0169-409X(89)90018-5.

Lochhead JJ, Thorne RG. 2012. Intranasal delivery of biologics to the central nervous system. Advanced Drug Delivery Reviews. 64(7):614-28. doi: 10.1016/j.addr.2011.11.002.

Lochhead JJ, Thorne RG. 2014. Capítulo 14: intranasal drug delivery to the brain. En: Hammarlund-Udenaes M, Lange ECM, Thorne RG & Editors Drug Delivery to the Brain: Physiological Concepts, Methodologies and Approaches. 1st edition. New York. aapspress. Springer. pp. 401-32.

Lopes T, Dias JS, Marcelino J, Varela J, Ribeiro S, Dias J. 2001. An assessment of the clinical efficacy of intranasal desmopressin spray in the treatment of renal colic. BJU International. 87(4):322-5. doi.org/10.1046/j.1464-410x.2001.00068.x.

Luzzati V, Benoit E, Charpentier G, Vachette P. 2004. X-ray scattering study of pike olfactory nerve: Elastic, thermodynamic and physiological properties of the axonal membrane. Journal of Molecular Biology. 343(1):199-212. doi: 10.1016/j.jmb.2004.08.029.

McMartin C, Hutchinson LE, Hyde R, Peters GE. 1987. Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity. Journal of Pharmaceutical Sciences. 76(7):535-40. doi: 10.1002/jps.2600760709.

Morimoto K, Miyazaki M, Kakemi M. 1995. Effects of proteolytic enzyme inhibitors on nasal absorption of salmon calcitonin in rats. International Journal of Pharmaceutics. 113(1):1-8. doi.org/10.1016/0378-5173(94)00158-2.

Nonaka N, Farr SA, Kageyama H, Shioda S, Banks WA. 2008. Delivery of galanin-like peptide to the brain: Targeting with intranasal delivery and cyclodextrins. Journal of Pharmacology and Experimental Therapeutics. 325(2):513-19. doi: 10.1124/jpet.107.132381.

Perl PD, Good PF. 1987. Uptake of aluminium into central system along nasal-olfactory pathways. The Lancet. 329(8540):1028. doi.org/10.1016/S0140-6736(87)92288-4.

Pollock H, Hutchings M, Weller RO, Zhang ET. 1997. Perivascular spaces in the basal ganglia of the human brain: Their relationship to lacunes. Journal of Anatomy. 191:337-46. doi: 10.1046/j.1469-7580.1997.19130337.x.

Rennels ML, Gregory TF, Blaumanis OR, Fujimoto K, Grady PA. 1985. Evidence for a ’paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Research. 326(1):47-63. doi.org/10.1016/0006-8993(85)91383-6.

Romeo VD, deMeireles J, Sileno AP, Pimplaskar, HK, Behl CR. 1998. Effects of physicochemical properties and other factors on systemic nasal drug delivery. Advanced Drug Delivery Reviews. 29(1-2):89-116. doi.org/10.1016/S0169-409X(97)00063-X.

Ross TM, Martinez PM, Renner JC, Thorne RG, Hanson LR, Frey WH 2nd. 2004. Intranasal administration of interferon beta bypasses the bloodbrain barrier to target the central nervous system and cervical lymph nodes: A non-invasive treatment strategy for multiple sclerosis. Journal of Neuroimmunology. 151(1-2):66-77. doi: 10.1016/j.jneuroim.2004.02.011.

Schaefer ML, Böttger B, Silver WL, Finger TE. 2002. Trigeminal collaterals in the nasal epithelium and olfactory bulb: A potential route for direct modulation of olfactory information by trigeminal stimuli. Journal of Comparative Neurology. 444(3):221-6. doi:10.1002/cne.10143.

Schley D, Carare-Nnadi R, Please CP, Perry VH, Weller RO. 2006. Mechanisms to explain the reverse perivascular transport of solutes out of the brain. Journal of Theoretical Biology. 238(4):962-74. doi: 10.1016/j.jtbi.2005.07.005.

Serralheiro A, Alves G, Fortuna A, Falcão A. 2014. Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting. European Journal of Pharmaceutical Sciences. 60:32-9. doi: 10.1016/j.ejps.2014.04.019.

Sharma S, Lohan S, Murthy, RSR. 2014. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery. Drug Development and Industrial Pharmacy. 40(7):869-78. doi: 10.3109/03639045.2013.789051.

Singh M, Vajdy M, Gardner J, Briones M, O’Hagan D. 2001. Mucosal immunization with HIV-1 gag DNA on cationic microparticles prolongs gene expression and enhances local and systemic immunity. Vaccine. 20(3-4):594-602. doi.org/10.1016/S0264-410X(01)00321-8

Soane RJ, Frier M, Perkins AC, Jones NS, Davis SS, Illum L. 1999. Evaluation of the clearance characteristics of bioadhesive systems in humans. International Journal of Pharmaceutics. 178(1):55-65. https://doi.org/10.1016/S0378-5173(98)00367-6

Syeilla VD, Leah R H, William HF. 2009. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. Wiley InterScience (www.interscience.wiley.com). doi: 10.1002/jps.21924

Tayebati SK, Nwankwo IE, Amenta F. 2012. Intranasal drug delivery to the central nervous system: present status and future outlook. Current Pharmaceutical Design. 19(3):510-26. doi:10.2174/1381612811306030510

Thorne RG, Emory CR, Ala TA, Frey WH 2nd. 1995. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Research. 692(1-2):278-82. doi.org/10.1016/0006-8993(95)00637-6

Thorne RG, Pronk GJ, Padmanabhan V, Frey WH 2nd. 2004. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience. 127(2):481-96. doi: 10.1016/j.neuroscience.2004.05.029

Thorne RG, Frey WH 2nd. 2001. Delivery of neurotrophic factors to the central nervous system: Pharmacokinetic considerations. Clinical Pharmacokinetics. 40(12):907-46. doi: 10.2165/00003088-200140120-00003

Velin D, Kraehenbuhl JP. 2000. Delivery systems and adjuvants for vaccination against HIV. Pathobiology EXS. 89:227-37.

Walter BA, Valera VA, Takahashi S, Matsuno K, Ushiki T. 2006. Evidence of antibody production in the rat cervical lymph nodes after antigen administration into the cerebrospinal fluid. Archives of Histology and Cytology. 69(1):37-47. doi.org/10.1679/aohc.69.37

Wheatley MA, Dent J, Wheeldon EB, Smith PL. 1988. Nasal drug delivery: An in vitro characterization of transepithelial electrical properties and fluxes in the presence or absence of enhancers. Journal of Controlled Release. 8(2):167-77. doi.org/10.1016/0168-3659(88)90043-0

Yuki Y, Byun Y, Fujita M, Izutani W, Suzuki T, Udaka S, Fujihashi K, McGhee JR, Kiyono H. 2001. Production of a recombinant hybrid molecule of cholera toxin‐B‐subunit and proteolipid‐protein‐peptide for the treatment of experimental encephalomyelitis. Biotechnology and Bioengineering. 74(1):62-9. doi.org/10.1002/bit.1095

Zhang ET, Richards HK, Kida S, Weller RO. 1992. Directional and compartmentalised drainage of interstitial fluid and cerebrospinal fluid from the rat brain. Acta Neuropathologica. 83(3):233-9.

Cómo citar
Velloso, M. I., Ferreira, V., Vita, M., & Landoni, M. F. (2019). Vía intranasal: una alternativa para la administración de fármacos de acción central en equinos. Analecta Veterinaria, 39(1), 033. https://doi.org/10.24215/15142590e033
Revisiones bibliográficas