Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

Tatiana N. Pashirova, Irina V. Zueva, Konstantin A. Petrov, Svetlana S. Lukashenko, Irek R. Nizameev, Natalya V. Kulik, Aleksandra D. Voloshina, Laszlo Almasy, Marsil K. Kadirov, Patrick Masson, Eliana B. Souto, Lucia Ya Zakharova, Oleg G. Sinyashin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

New mixed cationic liposomes based on L-α-phosphatidylcholine and dihexadecylmethylhydroxyethylammonium bromide (DHDHAB) were designed to overcome the BBB crossing by using the intranasal route. Synthesis and self-assembly of DHDHAB were performed. A low critical association concentration (0.01 mM), good solubilization properties toward hydrophobic dye Orange OT and antimicrobial activity against gram-positive bacteria Staphylococcus aureus (MIC=7.8 μg mL–1) and Bacillus cereus (MIC=7.8 μg mL–1), low hemolytic activities against human red blood cells (less than 10%) were achieved. Conditions for preparation of cationic vesicles and mixed liposomes with excellent colloidal stability at room temperature were determined. The intranasal administration of rhodamine B-loaded cationic liposomes was shown to increase bioavailability into the brain in comparison to the intravenous injection. The cholinesterase reactivator, 2-PAM, was used as model drug for the loading in cationic liposomes. 2-PAM-loaded cationic liposomes displayed high encapsulation efficiency (∼ 90%) and hydrodynamic diameter close to 100 nm. Intranasally administered 2-PAM-loaded cationic liposomes were effective against paraoxon-induced acetylcholinesterase inhibition in the brain. 2-PAM−loaded liposomes reactivated 12 ± 1% of brain acetylcholinesterase. This promising result opens the possibility to use marketed positively charged oximes in medical countermeasures against organophosphorus poisoning for reactivation of central acetylcholinesterase by implementing a non-invasive approach, via the “nose-brain” pathway.

Original languageEnglish
Pages (from-to)358-367
Number of pages10
JournalColloids and Surfaces B: Biointerfaces
Volume171
DOIs
Publication statusPublished - Nov 1 2018

Keywords

  • Acetylcholinesterase
  • Cationic liposomes
  • Drug delivery systems
  • Organophosphorus agent
  • Paraoxon
  • Pralidoxime chloride
  • Self-assembly
  • Surfactant

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

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  • Cite this

    Pashirova, T. N., Zueva, I. V., Petrov, K. A., Lukashenko, S. S., Nizameev, I. R., Kulik, N. V., Voloshina, A. D., Almasy, L., Kadirov, M. K., Masson, P., Souto, E. B., Zakharova, L. Y., & Sinyashin, O. G. (2018). Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model. Colloids and Surfaces B: Biointerfaces, 171, 358-367. https://doi.org/10.1016/j.colsurfb.2018.07.049