Synthesis of highly functional polypeptides and polypeptoids via N-carboxyanhydride ring opening polymerization as drug delivery nanosystems

Abstract

In this work, N-carboxyanydride ring opening polymerization (NCA-ROP) has been widely explored and used as synthetic strategy for the synthesis of polypeptides and polypeptoids affording well-defined polymers with low polydispersity index. The versatility of this synthetic methodology allowed the obtainment of homopolymers and copolymers (block or random) with different topology (lineal, star or brush), character (hydrophilic, hydrophobic or amphiphilic) and charge (positive, negative or neutral) to generate highly functional compounds as potential drug delivery nano systems. In Chapter 1, the principles and the current state of nanomedicines, especially those in clinical trials, in the market and/or polypeptide-based nanoparticles (NP) are reviewed. In Chapter 2, the basis of NCA-ROP polymerization has been reviewed and the main issues related with the use of NCA as starting material have been studied.In Chapter 3, the virtues of NCA-ROP have been exploited for the design and synthesis of complex architectures based on polypeptides and polypeptoids to obtain high molecular weight compounds which present nanoscale size in aqueous solution. In Chapter 4, non-ionic amphiphilic PSar-VitE compounds have been synthetized and the potential biological applications of these compounds have been explored testing its use as solubilizer of hydrophobic drugs and as shielding lipid in LNP formulations.