Sodium hyaluronate as a mucoadhesive component in nasal formulation enhances delivery of molecules to brain tissue

Sándor Horvát, András Fehér, Hartwig Wolburg, Péter Sipos, Szilvia Veszelka, Andrea Tóth, Lóránd Kis, Anita Kurunczi, Gábor Balogh, Levente Kürti, István Eros, Piroska Szabó-Révész, Mária A. Deli

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Intranasal administration of molecules has been investigated as a non-invasive way for delivery of drugs to the brain in the last decade. Circumvention of both the blood-brain barrier and the first-pass elimination by the liver and gastrointestinal tract is considered as the main advantages of this method. Because of the rapid mucociliary clearance in the nasal cavity, bioadhesive formulations are needed for effective targeting. Our goal was to develop a formulation containing sodium hyaluronate, a well-known mucoadhesive molecule, in combination with a non-ionic surfactant to enhance the delivery of hydrophilic compounds to the brain via the olfactory route. Fluorescein isothiocyanate-labeled 4 kDa dextran (FD-4), used as a test molecule, was administered nasally in different formulations to Wistar rats, and detected in brain areas by fluorescent spectrophotometry. Hyaluronan increased the viscosity of the vehicles and slowed down the in vitro release of FD-4. Significantly higher FD-4 transport could be measured in the majority of brain areas examined, including olfactory bulb, frontal and parietal cortex, hippocampus, cerebellum, midbrain and pons, when the vehicle contained hyaluronan in combination with absorption enhancer. The highest concentrations of FD-4 could be detected in the olfactory bulbs, frontal and parietal cortex 4 h after nasal administration in the mucoadhesive formulation. Intravenous administration of a hundred times higher dose of FD-4 resulted in a lower brain penetration as compared to nasal formulations. Morphological examination of the olfactory system revealed no toxicity of the vehicles. Hyaluronan, a non-toxic biomolecule used as a mucoadhesive in a nasal formulation, increased the brain penetration of a hydrophilic compound, the size of a peptide, via the nasal route.

Original languageEnglish
Pages (from-to)252-259
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume72
Issue number1
DOIs
Publication statusPublished - May 2009

Fingerprint

Hyaluronic Acid
Nose
Brain
Intranasal Administration
Parietal Lobe
Olfactory Bulb
Frontal Lobe
Mucociliary Clearance
Pons
Nasal Cavity
Spectrophotometry
Mesencephalon
Dextrans
Blood-Brain Barrier
Fluorescein
Surface-Active Agents
Viscosity
Intravenous Administration
Cerebellum
Gastrointestinal Tract

Keywords

  • Absorption enhancer
  • Blood-brain barrier
  • Brain targeting
  • FITC-dextran
  • Hyaluronic acid
  • In vitro drug release
  • Mucoadhesive
  • Nasal drug delivery
  • Rheology

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Cite this

Sodium hyaluronate as a mucoadhesive component in nasal formulation enhances delivery of molecules to brain tissue. / Horvát, Sándor; Fehér, András; Wolburg, Hartwig; Sipos, Péter; Veszelka, Szilvia; Tóth, Andrea; Kis, Lóránd; Kurunczi, Anita; Balogh, Gábor; Kürti, Levente; Eros, István; Szabó-Révész, Piroska; Deli, Mária A.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 72, No. 1, 05.2009, p. 252-259.

Research output: Contribution to journalArticle

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