Surface charge modulation of poly(ethylene glycol)-poly(D, L-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 alpha-acetoxy-poly(ethylene glycol)-poly(D,L-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 (mu(2)/<(Gamma)over bar>(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. (C) 1999 Elsevier Science B.V. All rights reserved.