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Pharmaceutical Chemistry Journal

, Volume 53, Issue 2, pp 89–100 | Cite as

Prospects for Intranasal Delivery of Neuropeptides to the Brain

  • K. V. ShevchenkoEmail author
  • I. Yu. Nagaev
  • L. A. Andreeva
  • V. P. Shevchenko
  • N. F. Myasoedov
MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION
  • 13 Downloads

Intranasal administration (INA) of medicines has the advantages of being noninvasive, painless, simple, and convenient. The basic approaches to solving problems with effective delivery of peptides to the brain through nasal membranes are discussed with respect to nasal cavity anatomy and physiology. INA can bypass the blood—brain barrier although proteolysis of the peptides by olfactory epithelium components, i.e., the enzyme barrier, is an obstacle. Pro-Gly-Pro, Pro-Gly-Pro-Leu, Semax, and Selank were used as reference peptides for in vivo experiments. The maximum contents in rat blood plasma of Pro-Gly-Pro-Leu, Semax, Pro-Gly-Pro, and Selank were 0.54, 1.69, 1.30, and 1.04%, respectively, of the administered amount of labeled peptide. The corresponding values in rat brain for Pro-Gly-Pro-Leu, Semax, Pro-Gly-Pro, and Selank reached 0.0013, 0.13, 0.04, and 0.16%. The methionine in Semax was replaced by alanine, glycine, threonine, and tryptophan to minimize its proteolysis during transversal of the enzyme barrier. Liposomes and acetylation of the N-terminal amino acids were also used to improve the stability of Semax. Use of N-acetyl-Semax was shown to be most promising. In vitro experiments used leucine aminopeptidase (incubation medium contained 12.6% Semax after 60 min), dipeptidyl peptidase (95.4%), carboxypeptidases B (96.8%) and Y(51.0%), nasal mucus enzymes (4.0%), and microsomal fractions of rat brain (9.0%) and blood plasma (0.7%). Proteolysis of Semax formed mainly His-Phe-Pro-Gly-Pro, Phe-Pro-Gly-Pro, and Pro-Gly-Pro.

Keywords

intranasal administration enzyme barrier peptide proteolysis 

Notes

Acknowledgments

The work was partially sponsored by the RAS Presidium Basic Research Programs “Basic research for development of biomedical technologies” and “Molecular and cellular biology and post-genomic technologies.”

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • K. V. Shevchenko
    • 1
    Email author
  • I. Yu. Nagaev
    • 1
  • L. A. Andreeva
    • 1
  • V. P. Shevchenko
    • 1
  • N. F. Myasoedov
    • 1
  1. 1.Institute of Molecular Genetics, Russian Academy of Sciences (IMG RAS)MoscowRussia

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