Poly(lactic acid)/poly(ethylene glycol) supramolecular diblock copolymers based on three-fold complementary hydrogen bonds: Synthesis, micellization, and stimuli responsivity

Abstract

Thymine-terminated poly(lactic acid) (PLA-THY) and diaminotriazine-terminated poly(ethylene glycol) (PEG-DAT) are synthesized and they can form the supramolecular amphiphilic diblock copolymers in solution through the thymine/diaminotriazine complementary hydrogen bonding interactions. Such supramolecular copolymers self-assemble into the stimuli-responsive micelles in aqueous solution. Micelle size, crystalline state, stimuli responsibility, drug loading and release behavior of the supramolecular micelles can be readily tuned from the block length, stereostructure, homo and stereocomplex crystallizations of hydrophobic PLA blocks. The enantiomerically-mixed supramolecular copolymers with both poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) blocks assemble into the stereocomplexed micelles, while those having the isotactic PLLA (or PDLA) and atactic poly(d,l-lactic acid) (PDLLA) blocks form the homocrystalline and amorphous micelles, respectively. The stereocomplexed and amorphous micelles exhibit smaller size than their homocrystalline analogs, all of which are much larger than the micelles formed from the conventional covalently-bonded diblock copolymers. The supramolecular micelles are sensitive to the external stimuli such as pH and ion. The homocrystalline and stereocomplexed micelles undergo fast aggregation in the acidic and salted solutions due to the disassociation of complementary hydrogen bonds. The stereocomplexed micelles exhibit larger drug loading content and slower drug release rate than the amorphous and homocrystalline ones, because of the larger polymer/drug interactions and tighter chain packing inside the micelle cores.