Micelles formed by self-assembling of polylactide/poly(ethylene glycol) block copolymers in aqueous solutions

Abstract

Copolymers of polylactide (PLA) and poly(ethylene glycol) (PEG) were synthesized by ring-opening polymerization of l- or d-lactide in the presence of mono- or dihydroxyl PEG using nontoxic zinc lactate as catalyst. The resulting diblock and triblock copolymers were characterized by various analytical techniques such as SEC, 1H NMR, XRD, and DSC. Bioresorbable micelles were prepared from aqueous solutions of the various copolymers without using any organic solvent. The mixed micellar solutions containing both L-PLA/PEG and D-PLA/PEG copolymers appeared more stable than the separate solutions according to critical micellar concentration (CMC) results, which could be assigned to stronger interactions between L-PLA and D-PLA blocks. The properties of the polymeric micelles strongly depend on the chain structure and composition of the copolymers. CMC values in the presence of salt and at 37 °C suggested that the micelles could exhibit good stability in vivo. Thermodynamic parameters calculated from the dependence of CMC on temperature indicate that the micellization process is spontaneous and driven by entropy gain. Dynamic light scattering (DLS) measurements showed one or two populations of micelles for dilute and concentrated solutions, the micelle size decreasing upon dilution. TEM confirmed the presence of micelles, but the size estimated from TEM was smaller than that from DLS due to the dehydration and shrinkage during drying.