Polymers and peptide-polymer conjugates as bioactive platforms and carriers for the encapsulation of biomolecules

Resumen

In the last decade, conductive polymers have received great interest in both scientific and technological levels due to the electroactive properties exhibited by these materials. For this reason, the main aim of this Doctoral Thesis is to study the applications of some conducting polymers, mainly derived from polythiophene, in the field of biomedicine and biotechnology. According to the objectives proposed in this Document, different studies focused on the preparation and characterization of graft copolymers have been carried out using macromonomers formed by oligo-thiophenes to which PEG chains of well-defined molecular weight have been incorporated as substituents. After this, the behavior of these new polymers has been investigated in terms of cytotoxicity and biocompatibility using cell adhesion and cell proliferation assays. Then, the synthesis and characterization of conducting polymer-peptide hybrids have been developed. Initially, the methodology used for the preparation of these materials has been optimized using model systems in which the peptide has been replaced by an amino acid, which has been engineered by chemical similarity. After evaluate different synthetic approaches, hybrids constructed by combining the same conducting polymer and the RG*D peptide have been prepared, where RG*D is a sequence analogous to the RGD (Arg-Gly-Asp) in which the central Gly residue is replaced by the above mentioned engineered amino acids. The biocompatibility and the bioactivity of all these compounds have been examined. The last part of this thesis is oriented towards the encapsulation of small biomolecules in polymeric nanostructures that can be used as transport systems and controlled release systems when incorporated into the organism. The encapsulation of simple amino acids has been examined firstly, this research evolving towards the immobilization of linear and cyclic hydrophobic peptides. In all cases encapsulation was carried out by electrospraying or electrospinning. Results obtained in this Thesis have been reported in the following publications: - "Polythiophene-g-poly(ethylene glycol) Graft Copolymers from Electroactive Scaffolds". A.-D. Bendrea, G. Fabregat, J. Torras, S. Maione, L. Cianga, L. J. del Valle, I. Cianga & C. Alemán. J. Mater. Chem. B 2013, 1, 4135-4145. - "Effect of the Graft Ratio on the Properties of Polythiophene-g-poly(ethylene glycol)". S. Maione, G. Fabregat, L. J. del Valle, A.-D. Bendrea, L. Cianga, I. Cianga, F. Estrany & C. Alemán. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 239-252. - "Electro-Biocompatibility of Conjugates Designed by Chemical Similarity". S. Maione, G. Fabregat, L. J. del Valle, G. Ballano, C. Cativiela & C. Alemán. J. Pept. Sci. 2014, 20, 537-546. - "Electroactive Polymer-Peptide Conjugates for Adhesive Biointerfaces". S. Maione, A. M. Gil, G. Fabregat, L. J. del Valle, J. Triguero, A. Laurent, D. Jacquemin, F. Estrany, A. I. Jiménez, D. Zanuy, C. Cativiela & C. Alemán. Biomater. Sci. 2015, 3, 1395-1405. - Electrospray Loading and Release of Hydrophobic Gramicidin in Polyester Microparticles". S. Maione, L. J. del Valle, M. M. Pérez-Madrigal, C. Cativiela, J. Puiggalí & C. Alemán. RSC Adv. 2016, 6, 69634-69640. - "Biodegradable Nanofibrous Scaffolds as Smart Delivery Vehicles for Amino Acids". S. Maione, M. M. Pérez-Madrigal, L. J. Del Valle, A. Díaz, L. Franco, C. Cativiela, J. Puiggalí & C. Alemán. J. Appl. Polym. Sci. 2017, 134, 44883 (1-14).