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.
Highlights
The aim of this work is to synthesize cationic amphiphiles based on malonic acid amides
We have developed a synthesis scheme to produce new cationic amphiphiles with an asymmetric hydrophobic part
Our results demonstrate that the transfection efficiency of our liposomes is comparable to a commercial formulation
Summary
Катионные амфифилы на основе амидов малоновой кислоты в качестве медиаторов трансфекции. Задача данной работы заключалась в получении катионных амфифилов, являющихся амидами малоновой кислоты. Для таких катионных амфифилов должны быть определены физико-химические свойства и трансфекционная активность липосомальных композиций на их основе. В качестве второй гидрофобной цепи использовали N-олеиламин, который присоединяли по карбоксильной группе малоновой кислоты путем образования амидной связи. Полярная головная группа была представлена этилендиамином, который присоединяли по оставшейся карбоксильной группе малоновой кислоты. Размер полученных липосом позволяет им проникать в клетки, что делает возможным использование таких композиций для трансфекции. Катионные амфифилы на основе амидов малоновой кислоты являются перспективными для разработки трансфекционных липосомальных композиций на их основе. Ключевые слова: катионные липиды, амиды малоновой кислоты, катионные липосомы, трансфекционная активность, направленная доставка, катионные амфифилы.
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