Efficient Synthesis of Hydrophilic Hairy Semihollow Molecularly Imprinted Polymer Microcapsules with Ultrahigh Drug Loading and pH-Responsive Sustained Release Properties

A highly efficient approach to obtaining well-defined hydrophilic hairy semihollow molecularly imprinted polymer (MIP) microcapsules with ultrahigh drug loading and pH-responsive sustained release properties is described, which involves grafting of a thin propranolol-MIP layer and poly(2-hydroxyethyl methacrylate) (PHEMA) brushes onto the "living" poly(methacrylic acid) (PMAA) microspheres (prepared by one-pot reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization) via two-step surface-initiated RAFT polymerization and rapid etching of part of the PMAA core from the resulting core-shell-corona-structured MIP particles by methanol washing. Both the MIP layer thickness and etching degrees of the obtained core-shell-structured MIP particles could be easily tuned by adjusting the polymerization time, and the surface-grafting of PHEMA brushes was well-controlled. The unique structure of the semihollow MIP microcapsules with PMAA chains inside cavities endowed them with ultrahigh template loading capacities (1637 and 1065 μmol/g for MIP microcapsules without and with PHEMA brushes, respectively, which are much higher than those of the previously reported propranolol-MIPs (from dozens to 600 μmol/g)). Additionally, they showed high flexibility, obvious molecular imprinting effects, and extremely fast template binding kinetics (the semihollow MIP microcapsules without PHEMA brushes reaching equilibrium binding within 1 min). Furthermore, the pH-responsive sustained drug release of the propranolol-loaded hydrophilic hairy semihollow MIP microcapsules in PBS buffer solutions was also demonstrated. The high versatility of RAFT polymerization techniques and robust nature of the facile sacrificial PMAA core-etching method make our strategy a general and efficient way for developing advanced hydrophilic hairy semihollow MIP micro/nanocapsules highly promising in drug delivery and various bioanalytical applications.