The Reactive Polymeric Micelle, Convenient Tool for Targeting Drug Delivery System

Formation of amphiphilic poly(ethylene glycol)-b-polylactide (PEG/PLA) block copolymers was accomplished using potassium alkoxides to initiate the anionic polymerization of ethylene oxide, with the living chain end initiating the polymerization of lactide. Using potassium 3,3-diethoxypropoxide as an initiator, block copolymers with an acetal moiety at the PEG chain end, which was later converted into an aldehyde group, were obtained. Block copolymers were analyzed by H-NMR spectroscopy and GPC. The amphiphilic block copolymers formed micelles in aqueous milieu. The conversion of acetal end groups to aldehyde group was carried out by an acid treatment using 0.01 mol L^-1 hydrochloric acid. The extent of the conversion attained more than 90 % without any side reaction such as aldol condensation. The micellar structure may play an important role in preventing a possible aldol-condensation between two neighboring aldehyde groups at the PEG chain end. From a dynamic light scattering measurement, the micelle size and shape were estimated. No angular dependency of the scaled characteristic line width was observed in the case of acetal-PEG/PLA(52/56) micelle, suggesting a spherical structure. The diameter and polydispersity factor of the polymeric micelle were influenced by the molecular weights and the composition of the two components of the block copolymer. The block copolymer having a molecular weight of 5,200 for PEG and 5,600 for PLA was the most suitable balance for micelle formation with narrow distribution. Actually, the diameter and polydispersity factor (μ/Γ²) of the micelles from acetal-PEG/PLA(52/56) determined by the cumulant method were 33 nm and 0.03, respectively. No change in the micelle size and shape was observed before or after the conversion of the acetal end groups to aldehyde groups on the micelle. Critical association concentrations (cac) of polymeric micelles were characterized by fluorescence spectroscopy using pyrene as fluorescence probe. The cac was determined to be 2 - 4 mg L^-1. This functionalized micelle, in particular the one carrying terminal aldehyde groups, is expected to provide a new entity of supramolecular architechture as well as to have wide biomedical application in the fields of drug delivery, diagnosis and surface modification through the coupling of bioactive.