Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2008.05.016
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dc.titleDoxorubicin conjugated to d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS): Conjugation chemistry, characterization, in vitro and in vivo evaluation
dc.contributor.authorCao, N.
dc.contributor.authorFeng, S.-S.
dc.date.accessioned2014-10-09T06:46:10Z
dc.date.available2014-10-09T06:46:10Z
dc.date.issued2008-10
dc.identifier.citationCao, N., Feng, S.-S. (2008-10). Doxorubicin conjugated to d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS): Conjugation chemistry, characterization, in vitro and in vivo evaluation. Biomaterials 29 (28) : 3856-3865. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2008.05.016
dc.identifier.issn01429612
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/88775
dc.description.abstractTo develop a polymer-anticancer drug conjugate, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was employed as a carrier of doxorubicin (DOX) to enhance its therapeutic effects and reduce its side effects. Doxorubicin was chemically conjugated to TPGS. The molecular structure, drug loading efficiency, drug release kinetics and stability of the conjugate were characterized. The cellular uptake, intracellular distribution, and cytotoxicity were accessed by using MCF-7 breast cancer cells and C6 glioma cells as in vitro cell model. The conjugate showed higher cellular uptake efficiency and broader distribution within the cells. Judged by IC50, the conjugate was found 31.8, 69.6, 84.1% more effective with MCF-7 cells and 43.9, 87.7, 42.2% more effective with C6 cells than the parent drug after 24, 48, 72 h culture, respectively. The in vivo pharmacokinetics and biodistribution were investigated after an i.v. administration at 5 mg DOX/kg body weight in rats. Promisingly, 4.5-fold increase in the half-life and 24-fold increase in the area-under-the-curve (AUC) of DOX were achieved for the TPGS-DOX conjugate compared with the free DOX. The drug level in heart, gastric and intestine was significantly reduced, which is an indication of reduced side effects. Our TPGS-DOX conjugate showed great potential to be a prodrug of higher therapeutic effects and fewer side effects than DOX itself. © 2008 Elsevier Ltd. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.biomaterials.2008.05.016
dc.sourceScopus
dc.subjectCancer chemotherapy
dc.subjectChemotherapeutic engineering
dc.subjectDrug modification
dc.subjectPolymer-drug conjugation
dc.subjectProdrug
dc.typeArticle
dc.contributor.departmentCHEMICAL & BIOMOLECULAR ENGINEERING
dc.description.doi10.1016/j.biomaterials.2008.05.016
dc.description.sourcetitleBiomaterials
dc.description.volume29
dc.description.issue28
dc.description.page3856-3865
dc.description.codenBIMAD
dc.identifier.isiut000259017000012
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