Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms with Therapeutic Potential.
Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms with Therapeutic Potential.
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DOI：
10.1002/adhm.201700713
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发表时间：
2017-12
影响因子：
10
通讯作者：
Kloxin AM
中科院分区：
文献类型：
--
作者：
Kharkar PM;Scott RA;Olney LP;LeValley PJ;Maverakis E;Kiick KL;Kloxin AM
响应于生物学相关刺激的可注射药物递送系统为可定制的药物递送提供了有吸引力的策略。在这里，我们报告了独特的聚合物的设计和合成，用于创建原位形成的水凝胶，并响应于临床相关的内源性和外源性刺激而降解，特别是减少微环境和外部施加的光。使用迈克尔型加成反应用聚乙二醇和肝素基聚合物形成水凝胶。研究了所得水凝胶对低分子量蛋白质（例如，生长因子和细胞因子），其对于在体内调节各种细胞功能和命运是有意义的，但仍然难以递送。还原敏感的联系和光降解的联系的公司提供了显着的变化，在还原剂谷胱甘肽或光的存在下，分别在成纤维细胞生长因子-2（FGF-2）的释放曲线。释放的FGF-2的生物活性与原始FGF-2相当，表明这些水凝胶在包封和释放期间保持货物分子的生物活性的能力。此外，体内研究表明FGF-2的降解介导的释放。总的来说，我们的研究表明，这些独特的刺激响应化学控制低分子量蛋白质的局部释放，以响应临床相关的刺激的潜力。
Injectable drug delivery systems that respond to biologically relevant stimuli present an attractive strategy for tailorable drug delivery. Here, we report the design and synthesis of unique polymers for the creation of hydrogels that are formed in situ and degrade in response to clinically relevant endogenous and exogenous stimuli, specifically reducing microenvironments and externally applied light. Hydrogels were formed with polyethylene glycol and heparin-based polymers using a Michael-type addition reaction. The resulting hydrogels were investigated for the local controlled release of low molecular weight proteins (e.g., growth factors and cytokines), which are of interest for regulating various cellular functions and fates in vivo yet remain difficult to deliver. Incorporation of reduction-sensitive linkages and light-degradable linkages afforded significant changes in the release profiles of fibroblast growth factor-2 (FGF-2) in the presence of the reducing agent glutathione or light, respectively. The bioactivity of the released FGF-2 was comparable to pristine FGF-2, indicating the ability of these hydrogels to retain the bioactivity of cargo molecules during encapsulation and release. Further, in vivo studies demonstrated degradation-mediated release of FGF-2. Overall, our studies demonstrate the potential of these unique stimuli-responsive chemistries for controlling the local release of low molecular weight proteins in response to clinically relevant stimuli.
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影响因子：
3.7
作者：
Lin CC;Anseth KS
通讯作者：
Anseth KS
DOI：
10.1002/jbm.a.33106
发表时间：
2011-08
期刊：
Journal of biomedical materials research. Part A
影响因子：
--
作者：
Fu Y;Kao WJ
通讯作者：
Kao WJ
影响因子：
4.9
作者：
Bal, Tugba;Kepsutlu, Burcu;Kizilel, Seda
通讯作者：
Kizilel, Seda
影响因子：
29.4
作者：
Annabi, Nasim;Tamayol, Ali;Uquillas, Jorge Alfredo;Akbari, Mohsen;Bertassoni, Luiz E.;Cha, Chaenyung;Camci-Unal, Gulden;Dokmeci, Mehmet R.;Peppas, Nicholas A.;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali
影响因子：
4.8
作者：
Ashikari- Hada, S;Habuchi, H;Kimata, K
通讯作者：
Kimata, K