Cyclodextrin-based self-assembled supramolecular hydrogels and cationic polyrotaxanes for drug and gene delivery applications

Abstract

The supramolecular self-assembly between cyclodextrins (CDs) and polymers has been used for the development of novel supramolecular hydrogels and polyrotaxanes for drug and gene delivery applications. So far, a lot of supramolecular hydrogels have been formed between CDs and poly(ethylene oxide) or its copolymers. The supramolecular hydrogels are thixotropic and reversible, and can be injected through a needle from a syringe to form injectable drug delivery systems. In order to develop supramolecular hydrogels with better controlled release properties, suitable for long-term controlled release of drugs, the supramolecular hydrogels were formed by α-CD and various triblock copolymers where PEO blocks flank a hydrophobic middle block and where the extra intermolecular hydrophobic interaction of the middle blocks can further strengthen the hydrogel network. This induces the formation of more stable hydrogels for long-term controlled release of drugs. New cationic polyrotaxanes composed of multiple oligoethylenimine-grafted CDs threaded and end-capped on a block copolymer chain were designed and synthesized as a new class of polymeric gene delivery vectors, where the chain-interlocked cationic cyclic units formed an integrated supramolecular entity to function as a macromolecular gene vector. These supramolecular gene carriers have low cytotoxicity, strong DNA-binding capability, and high gene transfection efficiency. The development of the supramolecular hydrogels and gene carriers based on the inclusion complexation between CDs and polymers has opened up a new approach for designing novel drug and gene delivery systems.