Acid-degradable poly(ortho ester urethanes) copolymers for potential drug carriers: Preparation, characterization, in vitro and in vivo evaluation

被引:23
作者
Fu, Shengxiang [1 ]
Yang, Guanqing [1 ]
Wang, Jun [1 ]
Wang, Xin [1 ]
Cheng, Xu [1 ]
Tang, Rupei [1 ]
机构
[1] Anhui Univ, Sch Life Sci, Engn Res Ctr Biomed Mat, 111 Jiulong Rd, Hefei 230601, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
Ortho ester; Drug delivery; Antitumor; BLOCK-COPOLYMERS; SIDE-CHAINS; POLYMERIC MICELLES; CONTROLLED-RELEASE; ANTICANCER DRUGS; DELIVERY; NANOPARTICLES; PH; POLYURETHANE; DOXORUBICIN;
D O I
10.1016/j.polymer.2017.02.079
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
Herein, acid-degradable poly(ortho ester urethanes) (POEUs) were synthesized via polycondensation between an acid-labile ortho ester diamine and active esters of poly(e-caprolactone) (PCL) diols with different molecular weights. The POEUs nanoparticles were easily fabricated using an oil-in-water emulsion technique, whose ortho ester bonds in main-chains could be degraded at different rate in acidic pHs. DOX was loaded into the nanoparticles with high drug loading efficiency. In vitro release studies demonstrate that DOX is released in a pH-dependent manner. In vitro cellular uptake confirms that DOX-loaded POEUs nanoparticles can be more readily internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS), resulting in efficient antitumor efficiency of cancer cells. In vivo biodistribution and antitumor effect were evaluated by H22 tumorbearing mice. The results demonstrate that DOX-loaded POEUs nanoparticles show a prolonged blood circulation time and improved accumulation in solid tumor, leading to enhanced therapeutic efficacy. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1 / 14
页数:14
相关论文
共 52 条
[1]   Biodegradable injectable polyurethanes: Synthesis and evaluation for orthopaedic applications [J].
Adhikari, Raju ;
Gunatillake, Pathiraja A. ;
Griffiths, Ian ;
Tatai, Lisa ;
Wickramaratna, Malsha ;
Houshyar, Shadi ;
Moore, Tim ;
Mayadunne, Roshan T. M. ;
Field, John ;
McGee, Margaret ;
Carbone, Tania .
BIOMATERIALS, 2008, 29 (28) :3762-3770
[2]   Acid-degradable polymers for drug delivery: a decade of innovation [J].
Binauld, Sandra ;
Stenzel, Martina H. .
CHEMICAL COMMUNICATIONS, 2013, 49 (21) :2082-2102
[3]   Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: Promises, progress and prospects [J].
Deng, Chao ;
Jiang, Yanjiao ;
Cheng, Ru ;
Meng, Fenghua ;
Zhong, Zhiyuan .
NANO TODAY, 2012, 7 (05) :467-480
[4]   One-step preparation of reduction-responsive poly(ethylene glycol)-poly (amino acid)s nanogels as efficient intracellular drug delivery platforms [J].
Ding, Jianxun ;
Shi, Fenghua ;
Xiao, Chunsheng ;
Lin, Lin ;
Chen, Li ;
He, Chaoliang ;
Zhuang, Xiuli ;
Chen, Xuesi .
POLYMER CHEMISTRY, 2011, 2 (12) :2857-2864
[5]   Self-assembly of biodegradable polyurethanes for controlled delivery applications [J].
Ding, Mingming ;
Li, Jiehua ;
Tan, Hong ;
Fu, Qiang .
SOFT MATTER, 2012, 8 (20) :5414-5428
[6]   Effects of the type of release medium on drug release from PLIGA-based microparticles: Experiment and theory [J].
Faisant, N. ;
Akiki, J. ;
Siepmann, F. ;
Benoit, J. P. ;
Siepmann, J. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2006, 314 (02) :189-197
[7]   Uptake and photo-toxicity of Foscan®, Foslip® and Fospeg® in multicellular tumor spheroids [J].
Gaio, Elisa ;
Scheglmann, Dietrich ;
Reddi, Elena ;
Moret, Francesca .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 2016, 161 :244-252
[8]   Mechanisms of polymer degradation and erosion [J].
Gopferich, A .
BIOMATERIALS, 1996, 17 (02) :103-114
[9]   In vivo biocompatibility of sulfonated PEO-grafted polyurethanes for polymer heart valve and vascular graft [J].
Han, Dong Keun ;
Park, Kwideok ;
Park, Ki Dong ;
Ahn, Kwang-Duk ;
Kim, Young Ha .
ARTIFICIAL ORGANS, 2006, 30 (12) :955-959
[10]   Micelles Based on Acid Degradable Poly(acetal urethane): Preparation, pH-Sensitivity, and Triggered Intracellular Drug Release [J].
Huang, Fushi ;
Cheng, Ru ;
Meng, Fenghua ;
Deng, Chao ;
Zhong, Zhiyuan .
BIOMACROMOLECULES, 2015, 16 (07) :2228-2236