Design and study of physicochemical properties and bioactivity of self-assembling calixarene and dihydropyridine hybrids for DNA delivery

Summary

The aim of this work is the elaboration of new kinds of nanoparticles formed by cationic amphiphilic 1,4- dihydropyridine (1,4-DHP) derivatives and amphiphillic calixarenes (calixarenes and 1,4-DHP hybrids) for development of potential transmembrane delivery agents in cooperation experience between research groups from Latvia and Ukraine.

This aim will be achieved by the implementation of the following objectives:

1. Synthesis of the original calixarenes building blocks
   • chloromethylcalix[4]arenes
   • aldehydocalixarenes
2. Design and synthesis of the original delivery systems with improved properties
   • amphiphilic anionic, cationic or zwitterionic calix[4]arenes
   • synthesis of calixarenes and 1,4-DHP hybrids
   • variations of number of DHP fragments in hybrid molecule structure
   • variations of lipophilic and hydrophilic part in hybrid molecule structure
3. Characterisation of self-assembling properties of new DNA delivery systems with improving properties
4. Study bioactivity of self-assembling calixarene and dihydropyridine hybrids
5. Study of delivering properties of calixarene and dihydropyridine hybrid nanoassociates as well as single molecules for lipophilic drug-like molecules
6. Dissemination of the results in SCI journals and international conferences at both countries.

Implementation of this project will give a contribution for the achieving the aims of the strategy of nanotechnology which is one of the six Key Enabling Technologies and has a significant impact on many different medicinal developments in the three main areas: Therapeutics, Diagnostics/Imaging and Regenerative Medicine as well as other related fields and topics in future.