title: Self-assembled micelles composed of doxorubicin conjugated Y-shaped PEG-poly(glutamic acid)2 copolymers via hydrazone linkers.
abstract: In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin)2 and linear copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose- and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y-shaped PEG-(polypeptide)2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Sui
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China. xuhui-spu@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Gou
authors.affiliation: Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Jingshuo
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, China. jinxq@jlu.edu.cn.
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Jin
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D018698:Glutamic Acid / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D006835:Hydrazones; D008823:Micelles; D010455:Peptides; D011108:Polymers; C097188:polyglutamine; D018698:Glutamic Acid; D004317:Doxorubicin