title: Thermoresponsive supramolecular micellar drug delivery system based on star-linear pseudo-block polymer consisting of β-cyclodextrin-poly(N-isopropylacrylamide) and adamantyl-poly(ethylene glycol).
abstract: Chemotherapy is facing several limitations such as low water solubility of anticancer drugs and multidrug resistance (MDR) in cancer cells. To overcome these limitations, a thermoresponsive micellar drug delivery system formed by a non-covalently connected supramolecular block polymer was developed. The system is based on the host-guest interaction between a well-defined β-cyclodextrin (β-CD) based poly(N-isopropylacrylamide) star host polymer and an adamantyl-containing poly(ethylene glycol) (Ad-PEG) guest polymer. The structures of the host and guest polymers were characterized by1H and13C NMR, GPC and FTIR. Subsequently, they formed a pseudo-block copolymer via inclusion complexation between β-CD core and adamantyl-moiety, which was confirmed by 2D NMR. The thermoresponsive micellization of the copolymer was investigated by UV-vis spectroscopy, DLS and TEM. At 37°C, the copolymer at a concentration of 0.2mg/mL in PBS formed micelles with a hydrodynamic diameter of ca. 282nm. The anticancer drug, doxorubicin (DOX), was successfully loaded into the core of the micelles with a loading level of 6% and loading efficiency of 17%. The blank polymer micelles showed good biocompatibility in cell cytotoxicity studies. Moreover, the DOX-loaded micelles demonstrated superior therapeutic effects in AT3B-1-N (MDR-) and AT3B-1 (MDR+) cell lines as compared to free DOX control, overcoming MDR in cancer cells.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors.forename: Xia
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors.forename: Jing-Ling
authors.initials: JL
authors.lastname: Zhu
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Singapore 138634, Singapore.
authors.forename: Zhong-Xing
authors.initials: ZX
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore. Electronic address: jun-li@nus.edu.sg.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D013696:Temperature; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D008823:Micelles; D047392:beta-Cyclodextrins; C052970:poly-N-isopropylacrylamide; D011092:Polyethylene Glycols; D004317:Doxorubicin; C031215:betadex; D000218:Adamantane
keywords: Doxorubicin; Drug delivery; Poly(N-isopropylacrylamide); Poly(ethylene glycol); β-Cyclodextrin