title: Temperature-related change in the properties relevant to drug delivery of poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles in aqueous milieu.
abstract: The block copolymers of poly(ethylene glycol) and poly(D,L-lactide) (PEG-PDLLA), the latter having a glass transition temperature (T(g)) around the physiological condition, was self-assembled into polymer micelles with a narrow and unimodal distribution in aqueous milieu either by dialysis or by the ultrasonication-aided dispersion method. The 1H NMR measurement of the PEG-PDLLA micelles in D(2)O revealed a gradual increase in the chain mobility of PDLLA segment in the core of the micelles at a temperature range above the T(g) of PDLLA. The critical association concentration (c.a.c.) of the PEG-PDLLA micelles was determined at various temperatures (25-55 degrees C) using pyrene as a probe to monitor the change in the polarity of the microenvironment in the micelle. An Arrhenius plot of the c.a.c. (ln(c.a.c.) versus 1/T) exhibited a break near T(g) of PDLLA. In sharp contrast with the linear decrease in ln(c.a.c.) versus 1/T in the region above the T(g), there was observed an almost constant c.a.c. (7-8 mg/l) regardless of the temperature change below the T(g). Furthermore, the chain exchange reaction between micelles was investigated based on the migration of the end-tagged block copolymers (alpha-lactosyl-PEG-PDLLA and omega-pyrenyl-PEG-PDLLA). The change in the binding affinity of the fluorescent micelles toward the RCA-1 lectin immobilized column was monitored with time to estimate the chain exchange. Consequently, appreciable acceleration in the chain exchange rate was revealed by increasing the surrounding temperature indicating the core mobility to be a substantial factor for inter-micellar chain migration. These results indicate that the engineering of the thermal characteristics of the core-forming segment of the block copolymer should be one of the crucial factors for optimizing the properties of the polymer micelles used for drug delivery.
authors.affiliation: Department of Materials Science, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasugi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Harada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D017666:Deuterium Oxide; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008970:Molecular Weight; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D013696:Temperature
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; C083464:poly(ethyleneglycol-lactide); D017666:Deuterium Oxide