Biosignal-sensitive polyion complex micelles for the delivery of biopharmaceuticals

The application of polyion complex (PIC) micelles into therapeutic fields is rapidly increasing due to simple and efficient encapsulation of biopharmaceuticals and outstanding biocompatibility among various polymer-based drug delivery carriers. Ionic biopharmaceuticals, such as DNA, RNA, and proteins can interact with ionic block copolymers to form PIC micelles with a core-shell structure. In this review, the development of smart PIC micelles that can respond to biosignals and the application of the biosignal-sensitive PIC micelles to the drug delivery are discussed. The change of ionic strength or pH-dependent protonation-deprotonation can be useful for the selective dissociation of PIC micelles because the ionic interaction between the block copolymer and counter-charged compounds is a main driving force for the formation of PIC micelles. The release of encapsulated biopharmaceuticals of PIC micelles can be effectively controlled by degradation of the chemical bonds in the block copolymer responding to the change of pH or reduction potential. Temperature-dependent hydrophilic-hydrophobic phase transition of block copolymers can also induce the destabilization of PIC micelles. Progress in smart PIC micelle as efficient, specific, and safe drug delivery system is indeed supported by the development of biosignal-sensitive block copolymers.