Intranasal delivery of human β-amyloid peptide in rats

Effective brain targeting

Eszter Sipos, Anita Kurunczi, András Fehér, Zsuzsa Penke, L. Fülöp, Ágnes Kasza, János Horváth, Sándor Horvát, S. Veszelka, G. Balogh, Levente Kürti, I. Erös, P. Szabó-Révész, A. Párducz, B. Penke, M. Deli

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)405-413
Number of pages9
JournalCellular and Molecular Neurobiology
Volume30
Issue number3
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Amyloid
Peptides
Olfactory Bulb
Brain
Nose
Frontal Lobe
Acetic Acid
Intranasal Administration
Long-Term Memory
Blood-Brain Barrier
Fluorescent Dyes
Short-Term Memory
Microscopy
Immunization
Spectrum Analysis
Anxiety
Central Nervous System
Costs and Cost Analysis
Water
Therapeutics

Keywords

  • β-Amyloid
  • Alzheimer's disease
  • Behavior
  • Nasal formulation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Intranasal delivery of human β-amyloid peptide in rats : Effective brain targeting. / Sipos, Eszter; Kurunczi, Anita; Fehér, András; Penke, Zsuzsa; Fülöp, L.; Kasza, Ágnes; Horváth, János; Horvát, Sándor; Veszelka, S.; Balogh, G.; Kürti, Levente; Erös, I.; Szabó-Révész, P.; Párducz, A.; Penke, B.; Deli, M.

In: Cellular and Molecular Neurobiology, Vol. 30, No. 3, 04.2010, p. 405-413.

Research output: Contribution to journalArticle

Sipos, Eszter ; Kurunczi, Anita ; Fehér, András ; Penke, Zsuzsa ; Fülöp, L. ; Kasza, Ágnes ; Horváth, János ; Horvát, Sándor ; Veszelka, S. ; Balogh, G. ; Kürti, Levente ; Erös, I. ; Szabó-Révész, P. ; Párducz, A. ; Penke, B. ; Deli, M. / Intranasal delivery of human β-amyloid peptide in rats : Effective brain targeting. In: Cellular and Molecular Neurobiology. 2010 ; Vol. 30, No. 3. pp. 405-413.
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