Cationic amphiphiles based on malonic acid amides as transfection mediators
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...
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MIREA - Russian Technological University
2020-11-01
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| Series: | Тонкие химические технологии |
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| Online Access: | https://www.finechem-mirea.ru/jour/article/view/1648 |
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| author | N. A. Romanova U. A. Budanova Yu. L. Sebyakin |
| author_facet | N. A. Romanova U. A. Budanova Yu. L. Sebyakin |
| author_sort | N. A. Romanova |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-462fda5a98c44d92a3bb6fade3ce3324 |
| institution | Matheson Library |
| issn | 2410-6593 2686-7575 |
| language | Russian |
| publishDate | 2020-11-01 |
| publisher | MIREA - Russian Technological University |
| record_format | Article |
| series | Тонкие химические технологии |
| spelling | doaj-art-462fda5a98c44d92a3bb6fade3ce33242025-08-04T10:19:39ZrusMIREA - Russian Technological UniversityТонкие химические технологии2410-65932686-75752020-11-01155364510.32362/2410-6593-2020-15-5-36-451608Cationic amphiphiles based on malonic acid amides as transfection mediatorsN. A. Romanova0U. A. Budanova1Yu. L. Sebyakin2MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)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.https://www.finechem-mirea.ru/jour/article/view/1648cationic lipidsmalonic acid amidescationic liposomestransfection efficiencytargeted deliverycationic amphiphiles |
| spellingShingle | N. A. Romanova U. A. Budanova Yu. L. Sebyakin Cationic amphiphiles based on malonic acid amides as transfection mediators Тонкие химические технологии cationic lipids malonic acid amides cationic liposomes transfection efficiency targeted delivery cationic amphiphiles |
| title | Cationic amphiphiles based on malonic acid amides as transfection mediators |
| title_full | Cationic amphiphiles based on malonic acid amides as transfection mediators |
| title_fullStr | Cationic amphiphiles based on malonic acid amides as transfection mediators |
| title_full_unstemmed | Cationic amphiphiles based on malonic acid amides as transfection mediators |
| title_short | Cationic amphiphiles based on malonic acid amides as transfection mediators |
| title_sort | cationic amphiphiles based on malonic acid amides as transfection mediators |
| topic | cationic lipids malonic acid amides cationic liposomes transfection efficiency targeted delivery cationic amphiphiles |
| url | https://www.finechem-mirea.ru/jour/article/view/1648 |
| work_keys_str_mv | AT naromanova cationicamphiphilesbasedonmalonicacidamidesastransfectionmediators AT uabudanova cationicamphiphilesbasedonmalonicacidamidesastransfectionmediators AT yulsebyakin cationicamphiphilesbasedonmalonicacidamidesastransfectionmediators |