Sugar-Installed Polymer Micelles:  Synthesis and Micellization of Poly(ethylene glycol)−Poly(d,l-lactide) Block Copolymers Having Sugar Groups at the PEG Chain End

A poly(ethylene glycol)−poly(d,l-lactide) block copolymer (PEG−PLA) having a site specifically protected-sugar group at the PEG chain end was synthesized through a successive ring-opening polymerization of ethylene oxide and d,l-lactide using a metalated protected sugar as an initiator. Removal of protective groups from the sugar residue in the block copolymer was quantitatively carried out using 80% trifluoroacetic acid at room temperature, yielding a block copolymer having a glucose or galactose residue at the chain end in a regioselective manner. Polymer micelles having sugar residues on the surface were then prepared by dialyzing an N,N-dimethylacetamide solution of the sugar-bearing PEG−PLA block copolymer against water. Dynamic light-scattering measurement of the polymer micelle solution revealed that the scaled characteristics line width had essentially no angular dependence, consistent with the spherical geometry of the polymer micelle. The diameter and polydispersity index of the polymer micelle, determined by a cumulant method, were approximately 40 nm and less than 0.1, respectively. Further, a galactose-bearing PEG−PLA micelle was confirmed to selectively attach to RCA-1 lectin, which is known to recognize β-d-galactose residues. These polymer micelles having sugar groups regioselectively on their exterior are expected to have wide utility in the field of drug delivery as glyco-receptor-directed carrier systems.