Cationic amphiphiles on the 1,4-dihydropyridine (1,4-DHP) scaffold with self-assembling properties form liposomes and can be used as transport systems. Our initial studies confirmed that some cationic 1,4-DHPs (e.g. comp. 1, Fig. 1) are more active than DOTAP and PEI 25 [1,2]. Last ten years we have been working on the development of compounds as gene delivery systems, studying the influence of lipids head-group on the gene transfection activity [3] and properties of formed liposomes [4]. The previous studies gave background for drawing of final conclusions concerning to relationships of biological and physical-chemical properties of liposomes forming compounds.
The aim of the work is to clarify the relationships of biological activity of self-assembling 1,4-DHPs and their physical-chemical properties: for individual compounds and their formed nanoaggregates.
To explore the posed questions we designed and synthesised a group of 1,4-DHP amphiphiles being structurally related to the most efficient delivery agent 1. The amphiphiles were synthesised by targeted modification of the substituents at the 1,4-DHP molecule, physical-chemical analysis of properties of them is performed. Characterisation of nanoaggregates was achieved by atomic force microscopy or transmission electron microscopy and the dynamic light scattering methods. The conclusions would be important for design and development of more efficient delivery agents.
Acknowledgements: Financial support by EuroNanoMed project ″CheTherDel″.
References: [1] Hyvönen Z., Plotniece A., Reine I., et al Biochim. Biophys. Acta, 2000, 1509, 451; [2] Hyvönen Z., Rönkkö S., Toppinen M.-R., et al J. Contr. Release, 2004, 99, 177; [3] Pajuste K., Hyvönen Z., Petrichenko O., et al New J. Chem., 2013, 37(10), 3062; [4] Rucins M., Petricenko O., Pajuste K., et al Adv. Materials Research, 2013, 787, 157.
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