Poly(amino acid)-grafted polymacrolactones. Synthesis, self-assembling and ionic coupling properties

Polyglobalide (PGl) with number average polymerization degree of ~20 was prepared by enzymatic ROP and then polyfunctionalized at 60% with aminothioethylene groups. The PGl₂₀-(NH₂)₁₂ copolymer was used as macroinitiator for the ROP of NCAs of BLG (γ-benzyl L-glutamate) and ZLL (^εN-carbobenzoxy-l-lysine) protected amino acids to produce neutral polypeptide-grafted polyglobalides poly[Gl₂₀-graft-(AA)_z] with z = 5 and 12, which upon deprotection, afforded anionic and cationic copolymers, respectively. Both protected and deprotected graft copolymers were characterized in full detail by NMR, and their thermal properties were evaluated by TGA and DSC. The structure of these copolymers in the solid-state was examined by FTIR and XRD using synchrotron radiation. All grafted polyglobalides were amorphous but the polypeptide side chains were arranged in either alpha-helix or beta-sheet conformation, and reliable indications on the occurrence of supramolecular structures were frequently found. The capacity of poly[Gl₂₀-graft-(AA)_z] copolymers to self-assemble in aqueous medium was evidenced by the preparation of well-shaped spheroidal nanoparticles with a diversity of sizes depending on copolymer composition and charge. Loading and release of doxorubicin (DOX) from nanoparticles made of negatively charged poly[Gl₂₀-graft-(LGA)₁₂] as well as DNA complexation with cationic poly[Gl₂₀-graft-(LL)₅] were explored to appraise the potential of these copolymers for building drug delivery systems.