Cyclodextrin-Responsive Micelles Based on Poly(ethylene glycol)-Polypeptide Hybrid Copolymers as Drug Carriers

Novel drug carriers based on poly(ethylene glycol) PEG-polypeptide copolymers, four-armed poly(epsilon-adamantane-L-lysine)(2)-block-poly(ethylene glycol)-block-poly-(epsilon-adamantane-L-lysine)(2) (PLys(Ad)(2)-b-PEG-b-PLys(Ad)(2)), have been prepared. The copolymers were synthesized via the ring-opening polymerization of amino acid N-carboxyanhydrides. The copolymers could spontaneously form core-shell micelles in aqueous solutions. It has been found that these micelles undergo triggered disassembly in response to an additional beta-cyclodextrin (beta-CD). The in vitro drug release beta-response to CD has been studied, and the result shows that the release of the entrapped drug doxorubicin (DOX) from the micelles could be accelerated by the addition of beta-CD. Their cytotoxicity and cell internalization behavior were also investigated in detail. These micelles are expected to have great potential in controlled drug release applications.