Preparation of mPEG-Hz-PLA Polymeric Micelles for pH Controlled Drug Delivery

您当前的位置：

首页 >

文章列表页 >

Preparation of mPEG-Hz-PLA Polymeric Micelles for pH Controlled Drug Delivery

Research Article | 更新时间：2021-03-19

|

- Preparation of mPEG-Hz-PLA Polymeric Micelles for pH Controlled Drug Delivery
- Acta Polymerica Sinica Issue 3, Pages: 482-490(2017)
- 作者机构：
  
  河南大学药物研究所开封 475004
- 作者简介：
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2017.16133
  CLC：
- Published：2017-3，
  
  Received：19 April 2016，
  
  Revised：13 June 2016，
扫描看全文
Luan Shu-juan, Xu Jing, Qi Pei-lan, Wang Kai, Wang Ying-ying, Song Shi-yong. Preparation of mPEG-Hz-PLA Polymeric Micelles for pH Controlled Drug Delivery. [J]. Acta Polymerica Sinica (3):482-490(2017)
DOI：

Luan Shu-juan, Xu Jing, Qi Pei-lan, Wang Kai, Wang Ying-ying, Song Shi-yong. Preparation of mPEG-Hz-PLA Polymeric Micelles for pH Controlled Drug Delivery. [J]. Acta Polymerica Sinica (3):482-490(2017) DOI： 10.11777/j.issn1000-3304.2017.16133.

摘要

以合成的含有腙键的聚乙二醇大分子（mPEG-Hz-OH）为引发剂，以丙交酯为单体引发开环聚合反应，并通过调整投料比，制备出3种不同分子量的含腙键的生物可降解嵌段聚合物（mPEG-Hz-PLA）.将腙键引入到聚合物的骨架中，以此构建聚合物胶束并作为pH敏感型纳米药物载体.制备的pH敏感型胶束的CMC值等于或低于5.46×10

4

mg/mL，DLS和TEM显示粒径均小于100 nm，且粒径分布均匀.非pH敏感型胶束在不同pH下的粒径变化不明显，而pH敏感型胶束在酸性环境下（pH=4.0和pH=5.0）胶束粒径出现了明显变化.以阿霉素为模型药物制备了pH敏感型载药胶束，其粒径比空白胶束大（100~200 nm），且粒径分布均匀.药物释放实验表明pH敏感型载药胶束随着释放介质pH降低累积释药量增高.MTT实验表明空白胶束对HeLa细胞和RAW264.7细胞几乎没有抑制作用，而载阿霉素的胶束对2种细胞的抑制作用都随着剂量的增大和时间的延长而增强.

Abstract

In some pH-sensitive drug delivery systems

hydrazone bonds frequently appeared in the side chains of the polymers as connections to doxorubicin (DOX). Introducing hydrazone bond onto the backbone of an amphiphilic copolymer to form pH-responsive hydrazone-containing micelles will realize the encapsulation of a broad spectrum of hydrophobic drugs. As a proof of concept

this work began with rational designing of mPEG-based macro-initiators and followed by ring-opening polymerization to construct hydrazone-containing biodegradable block polymers. A series of hydrazone-containing biodegradable copolymers (mPEG-Hz-PLA) of different molecular weights were synthesized. The diblock copolymers bear both hydrophilic PEG chain of fixed length and hydrophobic PLA chain of varied lengths. The resulting copolymers then self-assembled to form stable micelles with mean diameters below 100 nm. The study showed that these pH-sensitive polymeric micelles has a critical micelle concentration (CMC) of 5.46×10

4

mg/mL or less. Notable size change of the hydrazone-containing micelles were found after incubation in acidic media (pH=4.0 and 5.0)

while no size changes were observed for the polymeric micelles without hydrazone bonds. Doxorubicin (DOX) was used as the model drug and loaded into the core of micelles

leading to the micelles with a larger size (100-200 nm) than the blank ones. The drug loading content (DLC) and drug loading efficiency (DLE) of the micelles increased slightly along with the length of PLA. In vitro drug release study showed that DOX loaded in mPEG-Hz-PLA micelles were released more rapidly and more sufficiently under acidic conditions compared with non pH-sensitive micelles. Under pH=7.4

DOX released from both pH sensitive micelles and non-sensitive ones were less than 30% in 24 h. At pH 4.0

more than 70% of DOX was released from the pH-sensitive micelles while less than 45% of DOX released from the non-sensitive micelles in 24 h. MTT assay in HeLa and RAW264.7 cells lines showed enhanced antitumor ability for the DOX loaded pH sensitive micelles following 48 h incubation

compared with free DOX or non-sensitive micelles

while no obvious cytotoxicity was detected for the blank micelles. The hydrazone-containing micelles have great promise as a safe and effective carrier for antitumor drug delivery.

关键词

mPEG-Hz-PLA聚合物胶束pH敏感型药物释放

Keywords

mPEG-Hz-PLA polymerMicellespH-SensitiveDrug release

references

M Prabaharan , J J Grailer , S Pilla , D A Steeber , S Q Gong . . Biomaterials , 2009 . 30 ( 16 ): 3009 - 3019 . DOI:10.1016/j.biomaterials.2009.02.011http://doi.org/10.1016/j.biomaterials.2009.02.011.

Y H Tao , R Liu , M Q Chen , C Yang , X Y Liu . . J Mater Chem , 2012 . 22 ( 2 ): 373 - 380 . DOI:10.1039/C1JM13950Ahttp://doi.org/10.1039/C1JM13950A.

Yan Xiao , Yang Chen , Jinliang Yan , Meidong Lang . . Acta Polymerica Sinica , 2015 . ( 2 ): 228 - 235 . http://www.gfzxb.org/CN/abstract/abstract14245.shtml.

肖艳 , 陈洋 , 严金良 , 郎美东 . . 高分子学报 , 2015 . ( 2 ): 228 - 235 . http://www.gfzxb.org/CN/abstract/abstract14245.shtml.

S Hehir , N R Cameron . . Polym Int , 2014 . 63 ( 6 ): 943 - 954 . DOI:10.1002/pi.2014.63.issue-6http://doi.org/10.1002/pi.2014.63.issue-6.

M Huo , J Y Yuan , L Tao , Y Wei . . Polym Chem , 2014 . 5 ( 5 ): 1519 - 1528 . DOI:10.1039/C3PY01192Ehttp://doi.org/10.1039/C3PY01192E.

C Witschi , E Doelker . . J Control Release , 1998 . 51 ( 2-3 ): 327 - 341 . DOI:10.1016/S0168-3659(97)00188-0http://doi.org/10.1016/S0168-3659(97)00188-0.

V R Sinha , K Bansal , R Kaushik , R Kumria , A Trehan . . Int J Pharm , 2004 . 278 ( 1 ): 1 - 23 . DOI:10.1016/j.ijpharm.2004.01.044http://doi.org/10.1016/j.ijpharm.2004.01.044.

A Vonarbourg , C Passirani , P Saulnier , J P Benoit . . Biomaterials , 2006 . 27 ( 24 ): 4356 - 4373 . DOI:10.1016/j.biomaterials.2006.03.039http://doi.org/10.1016/j.biomaterials.2006.03.039.

S I Jeon , J H Lee , J D Andrade , Gennes P G de . . J Colloid Interf Sci , 1991 . 142 ( 1 ): 149 - 158 . DOI:10.1016/0021-9797(91)90043-8http://doi.org/10.1016/0021-9797(91)90043-8.

T McPherson , A Kidane , I Szleifer , K Park . . Langmuir , 1998 . 14 ( 1 ): 176 - 186 . DOI:10.1021/la9706781http://doi.org/10.1021/la9706781.

X Gao , F J Zheng , G Guo , X X Liu , R R Fan , Z Y Qian , N Huang , Y Q Wei . . J Mater Chem B , 2013 . 1 ( 42 ): 5778 - 5790 . DOI:10.1039/c3tb21091jhttp://doi.org/10.1039/c3tb21091j.

X J Zhang , D W Chen , S Ba , J Zhu , J Zhang , W Hong , X L Zhao , H Y Hu , M X Qiao . . Biomacromolecules , 2014 . 15 ( 11 ): 4032 - 4045 . DOI:10.1021/bm5010756http://doi.org/10.1021/bm5010756.

K T Oh , H Q Yin , E S Lee , Y H Bae . . J Mater Chem , 2007 . 17 ( 38 ): 3987 - 4001 . DOI:10.1039/b707142fhttp://doi.org/10.1039/b707142f.

M Talelli , K Morita , C J F Rijcken , R W M Aben , T Lammers , H W Scheeren , Nostrum C F van , G Storm , W E Hennink . . Bioconjugate Chem , 2011 . 22 ( 12 ): 2519 - 2530 . DOI:10.1021/bc2003499http://doi.org/10.1021/bc2003499.

J Chen , X Z Qiu , J Ouyang , J M Kong , W Zhong , M M Q Xing . . Biomacromolecules , 2011 . 12 ( 10 ): 3601 - 3611 . DOI:10.1021/bm200804jhttp://doi.org/10.1021/bm200804j.

K Sato , K Yoshida , S Takahashi , J Anzai . . Adv Drug Deliver Rev , 2011 . 63 ( 9 ): 809 - 821 . DOI:10.1016/j.addr.2011.03.015http://doi.org/10.1016/j.addr.2011.03.015.

D B Leeper , K Engin , A J Thistlethwaite , H D Hitchon , J D Dover , D J Li , L Tupchong . . Int J Radiat Oncol , 1994 . 28 ( 4 ): 935 - 943 . DOI:10.1016/0360-3016(94)90114-7http://doi.org/10.1016/0360-3016(94)90114-7.

Sluis R van , Z M Bhujwalla , N Raghunand , P Ballesteros , J Alvarez , S Cerdán , J P Galons , R J Gillies . . Magnet Reson Med , 1999 . 41 ( 4 ): 743 - 750 . DOI:10.1002/(ISSN)1522-2594http://doi.org/10.1002/(ISSN)1522-2594.

Y Wang , L M Dou , H J He , Y Zhang , Q Shen . . Mol Pharmaceutics , 2014 . 11 ( 3 ): 885 - 894 . DOI:10.1021/mp400547uhttp://doi.org/10.1021/mp400547u.

Q Yuan , W A Yeudall , H Yang . . Biomacromolecules , 2010 . 11 ( 8 ): 1940 - 1947 . DOI:10.1021/bm100589ghttp://doi.org/10.1021/bm100589g.

M Kong , H Park , X J Cheng , X G Chen . . J Control Release , 2013 . 172 ( 1 ): 281 - 291 . DOI:10.1016/j.jconrel.2013.08.022http://doi.org/10.1016/j.jconrel.2013.08.022.

Y N Xue , Z Z Huang , J T Zhang , M Liu , M Zhang , S W Huang , R X Zhuo . . Polymer , 2009 . 50 ( 15 ): 3706 - 3713 . DOI:10.1016/j.polymer.2009.05.033http://doi.org/10.1016/j.polymer.2009.05.033.

S X Lv , Z H Tang , D W Zhang , W T Song , M Q Li , J Lin , H Y Liu , X S Chen . . J Control Release , 2014 . 194 220 - 227 . DOI:10.1016/j.jconrel.2014.09.009http://doi.org/10.1016/j.jconrel.2014.09.009.

H S Yoo , T G Park . . J Control Release , 2001 . 70 ( 1-2 ): 63 - 70 . DOI:10.1016/S0168-3659(00)00340-0http://doi.org/10.1016/S0168-3659(00)00340-0.

H S Yoo , T G Park . . J Control Release , 2004 . 96 ( 2 ): 273 - 283 . DOI:10.1016/j.jconrel.2004.02.003http://doi.org/10.1016/j.jconrel.2004.02.003.

R P Tang , W H Ji , D Panus , R N Palumbo , C Wang . . J Control Release , 2011 . 151 ( 1 ): 18 - 27 . DOI:10.1016/j.jconrel.2010.12.005http://doi.org/10.1016/j.jconrel.2010.12.005.

更多指标>

0

Views

17

下载量

2

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Related Articles

Antibacterial Micelles Self-assembled from Copolypeptides through a One-step Acidification Process

Polyoxometalate-Polymer Composites for MR Imaging and Combined Photothermal-Chemotherapy

Preparation of Micelles and Gels via Polymerization of Pre-assembled Styrene and Polyacrylic Acid

Synthesis and Self-assembly of Hyperbranched Polymers

Synthesis and Photosensitivity of Spiropyran Hydroxypropylcellulose

Related Author

No data

Related Institution

Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University

Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University

Shanghai Key Laboratory of Advance Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University

Postal code：100190
Tel：010-62588927 Email：gfzxb@iccas.ac.cn
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05002797号-8 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰