Highly stable and degradable multifunctional microgel for self-regulated insulin delivery under physiological conditions

被引:58
作者
Zhang, Xinjie
Lu, Shaoyu
Gao, Chunmei
Chen, Chen
Zhang, Xuan
Liu, Mingzhu [1 ]
机构
[1] Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Peoples R China
基金
中国国家自然科学基金;
关键词
GLUCOSE-RESPONSIVE MICROGELS; CONTROLLED DRUG-DELIVERY; PH; HYDROGELS; RELEASE; POLYMERS; POLYMERIZATION; COMPLEXATION; TEMPERATURE; SENSITIVITY;
D O I
10.1039/c3nr00835e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (similar to 250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 degrees C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors.
引用
收藏
页码:6498 / 6506
页数:9
相关论文
共 53 条
[1]   Polysialic Acid-Based Micelles for Encapsulation of Hydrophobic Drugs [J].
Bader, Rebecca A. ;
Silvers, Angela L. ;
Zhang, Nan .
BIOMACROMOLECULES, 2011, 12 (02) :314-320
[2]   Microgels and microcapsules in peptide and protein drug delivery [J].
Bysell, Helena ;
Mansson, Ronja ;
Hansson, Per ;
Malmsten, Martin .
ADVANCED DRUG DELIVERY REVIEWS, 2011, 63 (13) :1172-1185
[3]   Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous silica nanoparticles for controlled drug release [J].
Chang, Baisong ;
Sha, Xianyi ;
Guo, Jia ;
Jiao, Yunfeng ;
Wang, Changchun ;
Yang, Wuli .
JOURNAL OF MATERIALS CHEMISTRY, 2011, 21 (25) :9239-9247
[4]   Synthesis of linear amphiphilic tetrablock quaterpolymers with dual stimulus response through the combination of ATRP and RAFT by a click chemistry site transformation approach [J].
Chen, Jiucun ;
Liu, Mingzhu ;
Gong, Honghong ;
Cui, Guangjun ;
Lu, Shaoyu ;
Gao, Chunmei ;
Huang, Feng ;
Chen, Tongtong ;
Zhang, Xinyu ;
Liu, Zhen .
POLYMER CHEMISTRY, 2013, 4 (06) :1815-1825
[5]   Modeling and comparison of dissolution profiles [J].
Costa, P ;
Manuel, J ;
Lobo, S .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2001, 13 (02) :123-133
[6]   Redox-cleavable star cationic PDMAEMA by arm-first approach of ATRP as a nonviral vector for gene delivery [J].
Dai, Fengying ;
Sun, Peng ;
Liu, Yongjie ;
Liu, Wenguang .
BIOMATERIALS, 2010, 31 (03) :559-569
[7]   Layer-by-layer multilayer films linked with reversible boronate ester bonds with glucose-sensitivity under physiological conditions [J].
Ding, Zhibo ;
Guan, Ying ;
Zhang, Yongjun ;
Zhu, X. X. .
SOFT MATTER, 2009, 5 (11) :2302-2309
[8]  
Duracher D, 1999, J POLYM SCI POL CHEM, V37, P1823
[9]   Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin [J].
Fan, Honglei ;
Huang, Jin ;
Li, Yaping ;
Yu, Jiahui ;
Chen, Jinghua .
POLYMER, 2010, 51 (22) :5107-5114
[10]   Charge-switching, amphoteric glucose-responsive microgels with physiological swelling activity [J].
Hoare, Todd ;
Pelton, Robert .
BIOMACROMOLECULES, 2008, 9 (02) :733-740