Synthesis and characterization of Di- and triblock copolymers of poly(ethylene oxide) and poly(DL-valine-co-DL-leucine)

Abstract

Di- and triblock copolymers of PEO and poly(DL-valine-co-DL-leucine) were prepared by polymerization of NCA mixtures of DL-valine and DL-leucine with amine-terminated PEO’s. These copolymers (PED-1~PET-3) were soluble in dichloroacetic acid, DMF and DMAc. Block copolymers (D1~T3) that have high contents of amino acid (higher than 30 mol%) showed low solubility in DMF and DMAc, indicating that the content of polypeptide is an important factor to control the solubility of PEO/polypeptide block copolymers. The synthesized block copolymers showed melting point shift to lower temperatures because attached polypeptide blocks at the end of PEO chains change the crystalline lamellar morphology of the PEO chains. These amphiphilic block copolymers formed various morphological phases such as nanosphere and multi-lamellar structures. Wide angle X-ray diffraction (WAXD) study showed the change in packing distance between the PEO chains on x-y plane after block polymerizations of triblock copolymer (PET-1). Diblock copolymers formed micelles and their aggregations were observed. While triblock copolymer formed the lamellar structures. This observation indicates that small polypeptide and large PEO contents makes the diblock copolymers form easily micelle structures whereas PEO centered triblock copolymers that have larger polypeptide content result in the formation of antiparallel lamellar structure because of easy phase separation. In the preliminary drug release study, critical micelle concentration (CMC) of diblock copolymer (PED-1) was determineded by employing pynene as an extrinsic probe and then the release of doxorubicin from the micelles decreased with an increase of poly(valine-co-leucine) (PVL) content because of stronger hydrophobic interaction between doxorubicin and polypeptide.