Synthesis of diblock copolymers of indomethacin/aspartic acid conjugated norbornenes and characterization of their self-assembled nanostructures as drug carriers

Abstract

© 2016 Elsevier Ltd Aspartic acid derived norbornene monomer 1 and indomethacin-conjugated norbornene monomer 2 were block copolymerized via ring-opening metathesis polymerization (ROMP) using the Grubbs 2nd generation ruthenium complexes. The block copolymers with number-average molecular weights ranging from 11,700 to 15,300 were obtained in good yields. Well-controlled structures of the block copolymers were verified by1H NMR and size exclusion chromatography (SEC) characterizations. The block composition significantly affected the solubility of the block copolymers in organic media.1H NMR spectroscopic, turbidity, and dynamic light scattering measurements revealed that poly(1)-block-poly(2) in the ratio of 1:2 = 50:50, 62:38 and 75:25 formed compound micelles with a diameter around 100 nm in a selective solvent, DMSO. The micelle size increased as the length of the poly(2) block increased. It was observed that the addition of water into the micelle solution resulted in the increase of the micelle size (around 1000 nm). TEM observation indicated that the sizes of the block copolymers were around 80–100 nm, and the formation of compound micelle clusters by the addition of water. Indomethacin was gradually released from the compound micelles after incubation in an acidic environment (pH = 3) at room temperature.