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

Abstract

Novel drug carriers based on poly(ethylene glycol) (PEG)-polypeptide copolymers, four-armed poly(ε-adamantane-l-lysine)₂-block-poly(ethylene glycol)-block-poly(ε-adamantane-l-lysine)₂ (PLys(Ad)₂-<i>b</i>-PEG-<i>b</i>-PLys(Ad)₂), have been prepared. The copolymers were synthesized via the ring-opening polymerization of amino acid <i>N</i>-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 β-cyclodextrin (β-CD). The in vitro drug release in response to β-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 β-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.