pH-responsive intermediary layer cross-linked micelles from zwitterionic triblock copolymers and investigation of their drug-release behaviors

Abstract

ABC-type triblock copolymers, namely poly[(ethylene glycol)methyl ether]-block-poly(tert-butyl methacrylate)-block-poly[2-N-(diisopropylamino)ethyl methacrylate] (MPEG-b-PBuMA-b-PDPA), were first synthesized and then the middle blocks were successfully converted into poly(methacrylic acid) to obtain MPEG-b-PMAA-b-PDPA zwitterionic triblock copolymers. These block copolymers were soluble in water and formed micellar aggregates with complex cores via hydrogen bonding interactions between MPEG and PMAA blocks below pH 4.0. When the pH was between 5.0 and 7.0, due to charge compensation between partially protonated PDPA and partially ionized PMAA blocks, micelles with polyion complex cores were observed. If the solution pH was above 8.0, deprotonation of tertiary amine groups provided a hydrophobic character to the PDPA block, which resulted in the formation of PDPAcore micelles while MPEG/anionic PMAA hybrid blocks formed hydrated coronas. Intermediary layer cross-linked (ILCL) micelles from PDPA-core micelles were also prepared by cross-linking the inner PMAA shell. The hydrophobic drug dipyridamole (DIP) was used to investigate the release profile of ILCL micelles. DIP can be loaded to the PDPA cores of the micelles in basic aqueous media. An increase in the degree of cross-linking causes slower release for the model drug. It was concluded that the more complex matrix formation in the intermediary layer of the micelles via cross-linking retards the drug release from the core.