title: pH-induced phase transition control of thermoresponsive nano-micelles possessing outermost surface sulfonamide moieties.
abstract: Diblock copolymer comprising thermoresponsive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PIPAAm-co-DMAAm) and hydrophobic poly(benzyl methacrylate) blocks was prepared by reversible addition-fragmentation chain transfer radical polymerization. Terminal functionalization of thermoresponsive blocks with either pH-responsive sulfadimethoxine (SD) or hydroxyl groups was performed through coupling reactions with thiol groups exposed by the aminolysis of dithiobenzoate groups located at P(IPAAm-co-DMAAm) termini. Outermost surface functionalized polymeric micelles were formed through the multi-assemblies of end-functional diblock copolymers with low critical micelle concentration (3.1-3.3 mg/L) regardless of their terminal groups. Variety of outermost surface functional groups had little influence on nano-scale diameters of approximately 19 nm at various pH values. Although the zeta-potentials of nonionic (phenyl and hydroxyl) surface micelles were independent of pH values ranged 8.1-5.4, those of SD-surface polymeric micelles changed from -12 to -4 mV with reducing pH value, which caused by the protonation of surface SD units (pK(a)=6.2). In addition, lower critical solution temperature (LCST) of SD-surface micelles significantly shifted from 38.6 to 22.6 °C with lowering pH from 5.4 to 8.1. These pH-induced lower LCST shifts were caused by extremely increasing surface hydrophobicity through the charge neutralization of SD moieties and the subsequent promoted dehydration of corona-forming polymer chains. These results indicated that the phase transition behavior of thermoresponsive nano-micelles was particularly controlled by modulating the properties of outermost surface chemistry via specific signals (e.g., pH, light, and biomolecular interaction).
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Shinjuku, Tokyo 162-8666, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kawahara
authors.forename: Jun
authors.initials: J
authors.lastname: Akimoto
authors.forename: Hideko
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D018625:Microscopy, Atomic Force; D044367:Phase Transition; D058105:Polymerization; D011109:Polymethacrylic Acids / Q000737:chemistry*; D013412:Sulfadimethoxine / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D008823:Micelles; D011109:Polymethacrylic Acids; C403811:poly(IPAAm-co-DMAAm); C098156:polybenzylmethacrylate; D013412:Sulfadimethoxine