title: A co-delivery system based on paclitaxel grafted mPEG-b-PLG loaded with doxorubicin: preparation, in vitro and in vivo evaluation.
abstract: Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX·HCl) based on methoxypoly(ethylene glycol)-block-poly(L-glutamic acid) (mPEG-b-PLG) for cancer treatment. PTX was grafted to the mPEG-b-PLG by esterification to give mPEG-b-PLG-g-PTX. DOX·HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX·HCl and mPEG-b-PLG-g-PTX in aqueous solution. The release rate of DOX·HCl from the drug-loaded nanoparticles (mPEG-b-PLG-g-PTX-DOX) was slow at blood pH (pH 7.4), but obviously increased at endosome pH (pH 5.4). The mPEG-b-PLG-g-PTX-DOX exhibited slight synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG-b-PLG-g-PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a 95.5% tumor-suppression-rate which was significantly higher than those of related single anticancer agents such as free DOX·HCl and mPEG-b-PLG-g-PTX. These results indicated that the mPEG-b-PLG-g-PTX-DOX would have great potential in cancer therapy.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Engineering College, Jiangxi Agriculture University, Nanchang 330045, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Shixian
authors.initials: S
authors.lastname: Lv
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: ztang@ciac.ac.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Engineering College, Jiangxi Agriculture University, Nanchang 330045, PR China. Electronic address: suikelmh@sina.com.
authors.forename: Muhua
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130012, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D065546:Drug Liberation; D004357:Drug Synergism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D004338:Drug Combinations; C579712:methoxypoly(ethylene glycol)-block-poly(glutamic acid); D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel
keywords: 4-Dimethylaminopyridine (PubChem CID 14284); Co-delivery; Diisopropylcarbodiimide (PubChem CID 12734); Dimethylsulfoxide-D6 (PubChem CID 75151); Doxorubicin; Doxorubicin (PubChem CID: 443939); Fluorescein isothiocyanate (PubChem CID 18730); Glutamic acid (PubChem CID 33032); Human breast cancer; N,N′-Dimethylformamide (PubChem CID 6228); Paclitaxel; Paclitaxel (PubChem CID: 441276); Poly(l-glutamic acid); Trifluoroacetic acid-d (PubChem CID 71502)