Síntesis de polímeros sensibles al medio para aplicaciones biomédicas y farmacéuticas.

The main purpose of the project developed in the University of Seville was the preparation of biodegradable and biocompatible polymers to study their potential biomedical and pharmaceutical applications. A series of homo- and co-polyurethanes have been successfully prepared from suitable functionalized monomers by polyaddition reactions. First, monomers derived from D-mannitol containing free hydroxyl groups to provide hydrophilicity to the polymers were prepared. On the other hand monomers containing disulfide bonds will ensure the degradation of the polymers under reductive environments. Degradation studies mediated by glutathione under physiological conditions as well as hydrolytic degradation showed that the hydrophilicity of the new materials was a determining factor in the degradation processes. Polyurethanes with the higher Dmannitol content were the most hydrophilic and those that degraded more effectively. Studies with selected polyurethanes forming matrix drug delivery systems have showed very promising control profiles with drug models under simulated gastrointestinal tract, specifically at the colon level. A series of triblock co-polyurethanes based on polyethylene glycol monomethyl ether have been successfully prepared. Preliminary selfassembly studies to obtain polymersomes have been carried out. Cationic polyurethanes based on L-arabinitol and D-mannitol have been prepared with protonatable amino groups able to interact with nucleic acids. DNA interaction studies demonstrated excellent polymer/DNA affinity, especially for the polymer based on D-mannitol, which also presented an excellent cytotoxicity profile. In this Thesis, 1,4- and 1,4/1,5-disubstituted cationic and non-cationic polytriazoles have been also synthesized by 1,3-dipolar cycloaddition reactions. These polytriazoles were obtained from diazide monomers based on D-mannitol and dialkyne monomers containing either protonatable amino or disulfide groups. In vitro transfection assays of the cationic polytriazoles with human embryonic stem cells have shown very promising results. The project developed in the University of Sheffield (UK) consisted of preparing a binary mixture of polyethylene glycol and poly(glycerol monomethacrylate) macro-chain transfer agents, which were chain-extended with poly(2-hydroxyethyl methacrylate) via Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization to prepare a series of block copolymer nanoparticles with different morphologies.