Surface charge modulation of poly(ethylene glycol)–poly( , -lactide) block copolymer micelles: conjugation of charged peptides

Block copolymer micelles with aldehyde functionality were prepared in aqueous medium by dialyzing the N,N-dimethylacetamide solution of α-acetoxy-poly(ethylene glycol)-poly( , -lactide) block copolymer (acetal-PEG–PDLLA) against water, followed by mild acid treatment to convert the acetal moiety of the micelle to the aldehyde group. Peptidyl ligands (phenylalanine (Phe) and tyrosyl–glutamic acid (Tyr–Glu)) were then chemically conjugated to the micelle through Schiff base formation and successive reductive amination using NaBH₃CN. Micelles with peptidyl ligands thus prepared have a size of approximately 40 nm with extremely narrow distribution (μ₂/ ²<0.1) based on cumulant analysis of dynamic light scattering. A maximum 53% of the PEG-chain end of the micelle could be converted into peptidyl groups. Zeta potential values of Tyr–Glu derivatized micelles were well correlated with the amount of conjugated ligands, controllable over the range of 0 to−9 mV in sodium phosphate buffer (pH 7.4, 10 mM). These micelles with peptidyl ligands may have a utility for exploring the effect of the surface charge on the pharmacokinetic behavior of particulate systems as well as for modulated drug delivery where cellular peptidyl receptors play a substantial role.