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Intranasal Delivery of Human β-Amyloid Peptide in Rats: Effective Brain Targeting

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Abstract

(1) Intranasal administration is a non-invasive and effective way for the delivery of drugs to brain that circumvents the blood–brain barrier. The aims of the study were to test a nasal delivery system for human β-amyloid (Aβ) peptides, to measure the delivery of the peptides to brain regions, and to test their biological activity in rats. (2) Aβ1-42, in the form of a mixture of oligomers, protofibrils, and fibrils was dissolved in a nasal formulation containing hydrophobic, hydrophylic, and mucoadhesive components. The peptide solution was administered intranasally to rats as a single dose or in repeated doses. (3) Nasally injected Aβ labeled with the blue fluorescent dye amino-methyl coumarinyl acetic acid (AMCA) could be detected by fluorescent microscopy in the olfactory bulb and frontal cortex. The concentration of the peptide was quantified by fluorescent spectroscopy, and a significant amount of AMCA-Aβ peptide could be detected in the olfactory bulb. Unlabeled Aβ also reached the olfactory bulb and frontal cortex of rats as evidenced by intense immunostaining. (4) In behavioral experiments, nasal Aβ treatment did not affect anxiety levels (open-field test) and short-term memory (Y-maze test), but significantly impaired long-term spatial memory in the Morris water maze. The treatments did not result in Aβ immunization. (5) The tested intranasal delivery system could successfully target a bioactive peptide into the central nervous system and provides a basis for developing a non-invasive and cost effective, new model to study amyloid-induced dysfunctions in the brain.

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Acknowledgments

We thank Dr. Csongor Ábrahám for the critical reading of the manuscript. This research was supported by grants from the Foundation of Gedeon Richter (for A.F. and S.V.), OTKA NK 73672, M36252, GVOP-KMA-52, FP-7 MEMOLOAD, FP-7 LIPIDIET.

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Authors and Affiliations

  1. Department of Medical Chemistry, University of Szeged, Szeged, Hungary

    Eszter Sipos, Zsuzsa Penke, Lívia Fülöp, Ágnes Kasza, János Horváth & Botond Penke

  2. Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62., 6726, Szeged, Hungary

    Anita Kurunczi, Sándor Horvát, Szilvia Veszelka, Árpád Párducz & Mária A. Deli

  3. Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary

    András Fehér, Sándor Horvát, Levente Kürti, István Erős & Piroska Szabó-Révész

  4. Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary

    Gábor Balogh

  5. Supramolecular and Nanostructured Materials Research Group, Hungarian Academy of Science, Szeged, Hungary

    Botond Penke

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  1. Eszter Sipos
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  2. Anita Kurunczi
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  3. András Fehér
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  4. Zsuzsa Penke
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  5. Lívia Fülöp
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  6. Ágnes Kasza
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  7. János Horváth
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  8. Sándor Horvát
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  9. Szilvia Veszelka
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  10. Gábor Balogh
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  11. Levente Kürti
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  12. István Erős
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  13. Piroska Szabó-Révész
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  14. Árpád Párducz
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  15. Botond Penke
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  16. Mária A. Deli
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Correspondence to Mária A. Deli.

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Sipos, E., Kurunczi, A., Fehér, A. et al. Intranasal Delivery of Human β-Amyloid Peptide in Rats: Effective Brain Targeting. Cell Mol Neurobiol 30, 405–413 (2010). https://doi.org/10.1007/s10571-009-9463-6

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  • DOI: https://doi.org/10.1007/s10571-009-9463-6

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