Experimental study of the liposomal form of fenoterol after improving the method of obtaining it

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Abstract

The effect of different concentrations of cryoprotector (sucrose) on the efficiency of fenoterol inclusion in the lipid matrix during lyophilization has been studied. It has been shown that the liposomal form with the content of cryoprotector in the internal environment of liposomes – 2.5 % and in the external environment equal to 2 % provides long-term preservation of the drug in the liposome cavity. Under these conditions, it is possible to achieve a monodisperse distribution of particles with an average diameter of 4.28±1.62 μm. The assumed quantitative composition of the cryoprotector ensures the manufacturability of the liposome production process, increases the stability of the lyophilizate structure and prevents the particles from sticking together, ensuring their uniformity.

The profile of two-stage release of fenoterol from the liposomal form has been shown in vitro. The first stage of rapid release was characterized by a transition to free form within 15 minutes to 42 % of the encapsulated fenoterol. At the second stage, the active principle was released more slowly for 480 minutes.

The model of bronchospasm induced by 1% histamine has shown the advantage of the liposomal form of fenoterol in comparison with its free form in the form of an aqueous solution. Intra-tracheal administration of the liposomal form of fenoterol at a dose of 17 ukg/kg provided for 360 minutes the preservation of external respiratory function at the level of initial values, despite histamine inhalation, while the duration of action of fenoterol did not exceed 120 minutes.

About the authors

Tatiana M. Ustinova

Institute of Military Medicine, Russian Federation of Ministry of Defense, Saint-Petersburg, Russia

Author for correspondence.
Email: gniiivm_15@mil.ru
ORCID iD: 0000-0001-9579-9190
SPIN-code: 7247-4663
Scopus Author ID: 57196118429

Ph.D. in Biology, Scientific Researcher at State Research Institute 

Russian Federation

Nikolai Vengerovich

State Research Institute of Military Medicine, Russian Federation of Ministry of Defense; Saint Petersburg State Chemical Pharmaceutical Universit of Ministry of health, St.-Petersburg

Email: nikolai.vengerovich@pharminnotech.com
ORCID iD: 0000-0003-3219-341X
SPIN-code: 6690-9649
Scopus Author ID: 55639823300
ResearcherId: U-3467-2019

Doctor of Medicine (MD), Professor of the Industrial Ecology Department, Deputy Head of Department, State Research Institute

Russian Federation

Mikhail A. Judin

State Scientific Research Test Institute of Military Medicine

Email: mikhail.judin@gmail.com
SPIN-code: 4763-9666
Scopus Author ID: 53265350500

Doctor of Medicine (MD),Assisting professor of Toxicology and Experimental Medicine Department, Chief of Department, State Research Institute of Military Medicine

Russian Federation

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Copyright (c) 2020 Ustinova T.M., Vengerovich N., Judin M.A.

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