Synthesis of pH-Responsive Chitosan Nanocapsules for the Controlled Delivery of Doxorubicin

被引:51
作者
Chen, Chih-Kuang [1 ,3 ]
Wang, Qing [1 ]
Jones, Charles H. [1 ]
Yu, Yun [1 ]
Zhang, Hanguang [1 ]
Law, Wing-Cheung [2 ]
Lai, Cheng Kee [1 ]
Zeng, Qinghang [1 ]
Prasad, Paras N. [2 ]
Pfeifer, Blaine A. [1 ]
Cheng, Chong [1 ]
机构
[1] SUNY Buffalo, Dept Chem & Biol Engn, Buffalo, NY 14260 USA
[2] SUNY Buffalo, Inst Lasers Photon & Biophoton, Buffalo, NY 14260 USA
[3] Feng Chia Univ, Dept Fiber & Composite Mat, Taichung 40724, Taiwan
基金
美国国家科学基金会;
关键词
DRUG-DELIVERY; BIODEGRADABLE NANOPARTICLES; GENE DELIVERY; CANCER-CELLS; POLYMERIC NANOPARTICLES; MULTIDRUG-RESISTANCE; CROSS-LINKING; CO-DELIVERY; CARRIERS; TUMOR;
D O I
10.1021/la4040485
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Well-defined chitosan nanocapsules (CSNCs) with tunable sizes were synthesized through the interfacial cross-linking of N-maleoyl-functionalized chitosan (MCS) in miniemulsions, and their application in the delivery of doxorubicin (Dox) was investigated. MCS was prepared by the amidation reaction of CS with maleic anhydride in water/DMSO at 65 degrees C for 20 h. Subsequently, thiol-ene cross-linking was conducted in oil-in-water miniemulsions at room temperature under UV irradiation for 1 h, using MCS as both a surfactant and precursor polymer, 1,4-butanediol bis(3-mercapto-propionate) as a cross-linker, and D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate as a cosurfactant. With the increase in cosurfactant concentration in the reaction systems, the sizes of the resulting CSNCs decreased steadily. Dox-loaded CSNCs were readily prepared by in situ encapsulation of Dox during miniemulsion cross-linking. With acid-labile beta-thiopropionate cross-linkages, the Dox-loaded CSNCs demonstrated a faster release rate under acidic conditions. Relative to free Dox, Dox-loaded CSNCs exhibited enhanced cytotoxicity toward MCF-7 breast cancer cells without any noticeable cytotoxicity from empty CSNCs. The effective delivery of Dox to MCF-7 breast cancer cells via Dox-loaded CSNCs was also observed.
引用
收藏
页码:4111 / 4119
页数:9
相关论文
共 59 条
[51]   Well-Defined Degradable Brush Polymer-Drug Conjugates for Sustained Delivery of Paclitaxel [J].
Yu, Yun ;
Chen, Chih-Kuang ;
Law, Wing-Cheung ;
Mok, Jorge ;
Zou, Jiong ;
Prasad, Paras N. ;
Cheng, Chong .
MOLECULAR PHARMACEUTICS, 2013, 10 (03) :867-874
[52]   Genetic toxicity and carcinogenicity studies of glutaraldehyde - a review [J].
Zeiger, E ;
Gollapudi, B ;
Spencer, P .
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2005, 589 (02) :136-151
[53]   Synthesis and Characterization of Thermally Responsive Pluronic F127-Chitosan Nanocapsules for Controlled Release and Intracellular Delivery of Small Molecules [J].
Zhang, Wujie ;
Gilstrap, Kyle ;
Wu, Laying ;
Bahadur, Remant K. C. ;
Moss, Melissa A. ;
Wang, Qian ;
Lu, Xiongbin ;
He, Xiaoming .
ACS NANO, 2010, 4 (11) :6747-6759
[54]   Biodegradable Nanoparticles Based on Linoleic Acid and Poly(β-malic acid) Double Grafted Chitosan Derivatives as Carriers of Anticancer Drugs [J].
Zhao, Ziming ;
He, Miao ;
Yin, Lichen ;
Bao, Jiamin ;
Shi, Lili ;
Wang, Bingqing ;
Tang, Cui ;
Yin, Chunhua .
BIOMACROMOLECULES, 2009, 10 (03) :565-572
[55]   Synthesis, characterization and cytotoxicity of photo-crosslinked maleic chitosan-polyethylene glycol diacrylate hybrid hydrogels [J].
Zhong, Chao ;
Wu, Jun ;
Reinhart-King, C. A. ;
Chu, C. C. .
ACTA BIOMATERIALIA, 2010, 6 (10) :3908-3918
[56]   Synthesis and Characterization of Amphiphilic Glycidol-Chitosan-Deoxycholic Acid Nanoparticles as a Drug Carrier for Doxorubicin [J].
Zhou, Huofei ;
Yu, Weiting ;
Guo, Xin ;
Liu, Xiudong ;
Li, Nan ;
Zhang, Ying ;
Ma, Xiaojun .
BIOMACROMOLECULES, 2010, 11 (12) :3480-3486
[57]   Poly(ethylene oxide)-block-Polyphosphoester-graft-Paclitaxel Conjugates with Acid-Labile Linkages as a pH-Sensitive and Functional Nanoscopic Platform for Paclitaxel Delivery [J].
Zou, Jiong ;
Zhang, Fuwu ;
Zhang, Shiyi ;
Pollack, Stephanie F. ;
Elsabahy, Mahmoud ;
Fan, Jingwei ;
Wooley, Karen L. .
ADVANCED HEALTHCARE MATERIALS, 2014, 3 (03) :441-448
[58]   Well-Defined Drug-Conjugated Biodegradable Nanoparticles by Azide-Alkyne Click Crosslinking in Miniemulsion [J].
Zou, Jiong ;
Yu, Yun ;
Yu, Lu ;
Li, Yukun ;
Chen, Chih-Kuang ;
Cheng, Chong .
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 2012, 50 (01) :142-148
[59]   Clicking Well-Defined Biodegradable Nanoparticles and Nanocapsules by UV-Induced Thiol-Ene Cross-Linking in Transparent Miniemulsions [J].
Zou, Jiong ;
Hew, Chyi Chin ;
Themistou, Efrosyni ;
Li, Yukun ;
Chen, Chih-Kuang ;
Alexandridis, Paschalis ;
Cheng, Chong .
ADVANCED MATERIALS, 2011, 23 (37) :4274-4277