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Cationic amphiphiles based on malonic acid amides as transfection mediators

https://doi.org/10.32362/2410-6593-2020-15-5-36-45

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Abstract

Objectives. The aim of this work is to synthesize cationic amphiphiles based on malonic acid amides. The target compounds should contain saturated and unsaturated alkyl chains in the hydrophobic portion, and one or two positive charges in the polar head as created by ethylenediamine and amino acid L-ornithine. For such cationic amphiphiles, we determined physicochemical properties and transfection efficiency of liposomes based on them.

Methods. The initial compound in the synthesis is diethylmalonate. We used C-alkylation to add the first hydrophobic chain (with octylbromide, dodecylbromide, or octadecylbromide). N-oleylamine was used as the second hydrophobic chain, which was attached at the carboxyl group of the malonic acid via amide bond formation. The polar head was represented by ethylenediamine, which was then attached at the second carboxyl group of the malonic acid. Further, L-ornithine was attached to ethylenediamine to produce cationic lipids with two positive charges in the head group. The structures of the compounds were characterized by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis. Particle size distribution was evaluated by photon correlation spectroscopy. The luciferase test was used to determine transfection efficiency using HeLa cells.

Results. We have developed a synthesis scheme to produce new cationic amphiphiles with an asymmetric hydrophobic part. The obtained liposomal particles are approximately 120 nm in size and have a relatively high zeta potential of 29–30 mV.

Conclusions. The size of these liposomes allows them to penetrate into cells, which makes it possible to use these compositions for transfection. The high zeta potential shows that the particles are stable. Our results demonstrate that the transfection efficiency of our liposomes (mixed with cholesterol) is comparable to a commercial formulation. Cationic amphiphiles based on malonic acid amides have great potential for liposome development for transfection.

About the Authors

N. A. Romanova
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)
Russian Federation

Nadezhda A. Romanova, Master Student, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medicinal and Organic Chemistry

86, Vernadskogo pr., Moscow, 119571, Russia



U. A. Budanova
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)
Russian Federation

Ulyana A. Budanova, Cand. of Sci. (Chemistry), Assistant, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medicinal and Organic Chemistry. Scopus Author ID 14622352500, ResearcherID E-1659-2014

86, Vernadskogo pr., Moscow, 119571, Russia



Yu. L. Sebyakin
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)
Russian Federation

Yury L. Sebyakin, Dr. of Sci. (Chemistry), Professor, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medicinal and Organic Chemistry. Scopus Author ID 6701455145, ResearcherID T-2835-2019

86, Vernadskogo pr., Moscow, 119571, Russia



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Supplementary files

1. Fig. 2. Transfection efficiency for obtained liposomes.
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Type Исследовательские инструменты
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2. This is to certify that the paper titled Cationic amphiphiles based on malonic acid amides as transfection mediators commissioned to us by Nadezhda A. Romanova, Ulyana A. Budanova, Yury L. Sebyakin has been edited for English language and spelling by Enago, an editing brand of Crimson Interactive Inc.
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  • A synthesis scheme was developed and new cationic amphiphiles with an asymmetric hydrophobic block were generated.
  • Liposomal dispersions were formed, and their physical and chemical properties and transfection activity were studied.
  • The obtained results indicate good potential of malonic acid amides for creating a new class of cationic amphiphiles used as transfection agents.

For citation:


Romanova N.A., Budanova U.A., Sebyakin Yu.L. Cationic amphiphiles based on malonic acid amides as transfection mediators. Fine Chemical Technologies. 2020;15(5):36-45. https://doi.org/10.32362/2410-6593-2020-15-5-36-45

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ISSN 2410-6593 (Print)
ISSN 2686-7575 (Online)