title: Dual-response nanocarrier based on graft copolymers with hydrazone bond linkages for improved drug delivery.
abstract: Core-shell micelles with biodegradability, thermo- and pH-response were successfully demonstrated by poly(2-oxepane-1,5-dione-co-epsilon-caprolactone) (P(OPD-co-CL)) grafted with hydrophilic segments of amine-terminated poly(N-isopropylacrylamide) (At-PNIPAM). To compare with the graft copolymer, P(OPD-co-CL) block PNIPAM polymer was also prepared. The micelles with core-shell structure were formed with both graft and block copolymers by self-assembly in aqueous solutions, of which PNIPAM shell is thermo-response. Furthermore, P(OPD-co-CL)-g-PNIPAM also showed pH-sensitivity, which was attributed to the acid-cleavable property of the hydrazone bond. The low critical micelle concentrations (CMCs) of graft polymers and block polymers were 6.7 mg/L and 14.3mg/L, respectively, which indicated the formation of stable micelles. Both drug-free and drug-loaded micelles were in uniformly spherical shape observed by transmission electron microscopy (TEM). The sizes of the drug-free and drug-loaded micelles prepared from graft polymer were 123.5 nm and 146.5 nm, respectively, and the sizes of those prepared from block polymer were 197.5 nm and 211.5 nm, respectively. The lower critical solution temperature (LCST) for the graft polymer was 34.3 degrees C, while that for the block polymer was 28.1 degrees C, demonstrating a thermo-response. The graft polymeric micelles exhibited thermo-triggered decelerated release at pH 7.4, and pH-triggered accelerated release at 25 degrees C in vitro release test, indicating that the graft polymeric micelles could be a promising site-specific drug delivery system for enhancing the bioavailability of the drug in targeted pathological areas.
authors.affiliation: Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. yyhe@mail.ecust.edu.cn
authors.forename: Yueying
authors.initials: Y
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Meidong
authors.initials: M
authors.lastname: Lang
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006835:Hydrazones / Q000737:chemistry*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D006835:Hydrazones; D008823:Micelles; D011108:Polymers; C052970:poly-N-isopropylacrylamide