Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers
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 chara...
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| Format: | Article |
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MDPI AG
2014-08-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/8/11915 |
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| author | Bowen Sui Hui Xu Jian Jin Jingxin Gou Jingshuo Liu Xing Tang Yu Zhang Jinghua Xu Hongfeng Zhang Xiangqun Jin |
| author_facet | Bowen Sui Hui Xu Jian Jin Jingxin Gou Jingshuo Liu Xing Tang Yu Zhang Jinghua Xu Hongfeng Zhang Xiangqun Jin |
| author_sort | Bowen Sui |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T14:13:59Z |
| format | Article |
| id | doaj.art-ce58a180c9a7406b95a91181cecfa300 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-14T14:13:59Z |
| publishDate | 2014-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ce58a180c9a7406b95a91181cecfa3002022-12-21T22:58:15ZengMDPI AGMolecules1420-30492014-08-01198119151193210.3390/molecules190811915molecules190811915Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone LinkersBowen Sui0Hui Xu1Jian Jin2Jingxin Gou3Jingshuo Liu4Xing Tang5Yu Zhang6Jinghua Xu7Hongfeng Zhang8Xiangqun Jin9Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, ChinaDepartment of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, ChinaDepartment of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, ChinaDepartment of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, ChinaSchool of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, ChinaDepartment of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, ChinaIn 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.http://www.mdpi.com/1420-3049/19/8/11915miktoarm-star copolymerconjugatedoxorubicinpH-responsive drug releasedrug delivery |
| spellingShingle | Bowen Sui Hui Xu Jian Jin Jingxin Gou Jingshuo Liu Xing Tang Yu Zhang Jinghua Xu Hongfeng Zhang Xiangqun Jin Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers Molecules miktoarm-star copolymer conjugate doxorubicin pH-responsive drug release drug delivery |
| title | Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers |
| title_full | Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers |
| title_fullStr | Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers |
| title_full_unstemmed | Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers |
| title_short | Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers |
| title_sort | self assembled micelles composed of doxorubicin conjugated y shaped peg poly glutamic acid 2 copolymers via hydrazone linkers |
| topic | miktoarm-star copolymer conjugate doxorubicin pH-responsive drug release drug delivery |
| url | http://www.mdpi.com/1420-3049/19/8/11915 |
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