Gelatin-based hydrogels with β-cyclodextrin as a dual functional component for enhanced drug loading and controlled release
Gelatin-based hydrogels with β-cyclodextrin as a dual functional component for enhanced drug loading and controlled release
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DOI：
10.1039/c3ra42532k
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发表时间：
2013-01-01
期刊：
影响因子：
3.9
通讯作者：
Li, Jun
中科院分区：
文献类型：
--
作者：
Liu, Chengde;Zhang, Zhongxing;Li, Jun
在本文中，我们展示了一种简单而实用的方法来制备化学交联明胶基水凝胶，使用β-环糊精（β-CD），发挥双重作用，作为交联剂以及增强抗癌药物甲氨蝶呤（MTX）的结合的主体分子，以实现高载药水平以及抗癌药物的控制和持续释放。为此目的，一系列新的β-CD交联明胶基水凝胶的合成和表征。水凝胶的β-CD含量为11- 15%，交联度为21- 36%。明胶基水凝胶在PBS缓冲液中溶胀良好。水凝胶水解降解，并通过在PBS缓冲液中的胶原酶加速降解。研究发现，无论使用何种交联剂，较高的含水量都会导致水凝胶更快的生物降解。以芘为荧光探针，研究了明胶基水凝胶的微环境。芘被很好地吸附在β-CD交联的水凝胶中，并且水凝胶中的芘分子被包含并络合在β-CD交联剂的疏水空腔内。研究了MTX在水凝胶中的吸附、负载、结合、络合和释放。通过将溶胀的水凝胶样品浸入MTX饱和水溶液中，将MTX吸附并负载到水凝胶中。通过测定MTX负载水凝胶的紫外-可见光谱证实MTX在水凝胶中的负载，光谱表明负载MTX在β-CD交联的水凝胶中与β-CD络合。我们的数据表明，MTX与β-CD交联剂的络合大大增加了MTX在水凝胶中的负载水平。复合也可以降低初始突释效应，然后延迟复合MTX的释放一段时间，直到水凝胶开始水解降解，所有剩余的MTX释放。由于独特的结构和性质，β-CD交联明胶基水凝胶表现出有趣的多相特性，用于MTX药物的控制和持续释放。因此，β-CD-交联明胶基水凝胶可用作抗癌药物的控制和持续释放以及局部递送的有希望的药物载体。
In this paper, we demonstrate a simple and practical method to prepare chemically crosslinked gelatin-based hydrogels using beta-cyclodextrin (beta-CD) that plays a dual role as a crosslinker as well as a host molecule for enhanced binding of anticancer drug methotrexate (MTX), to achieve high drug loading level as well as controlled and sustained release of the anticancer drug. For this purpose, a series of novel beta-CD-crosslinked gelatin-based hydrogels were synthesized and characterized. The beta-CD content of the hydrogels was 11-15%, and the crosslinking degree was 21-36%. The gelatin-based hydrogels could swell well in PBS buffer. The hydrogels degraded hydrolytically and the degradation was accelerated by collagenase in PBS buffer. It was found that the higher water content resulted in faster biodegradation of the hydrogels regardless of the crosslinker used. Pyrene was used as a fluorescence probe to investigate the micro-environment of the gelatin-based hydrogels. Pyrene was well adsorbed in the beta-CD-crosslinked hydrogels, and the pyrene molecules in the hydrogels were included and complexed within the hydrophobic cavities of the beta-CD crosslinkers. The adsorption, loading, binding and complexation, and release of MTX in or from the hydrogels were investigated. MTX was adsorbed and loaded into the hydrogels by immersing the swollen hydrogel samples in MTX saturated aqueous solution. The loading of MTX in the hydrogels was confirmed by measuring the UV-vis spectra of the MTX-loaded hydrogels, the spectra indicated that the loaded MTX was complexed by beta-CD in the beta-CD-crosslinked hydrogels. Our data showed that the complexation of MTX with beta-CD crosslinkers largely increased the loading level of MTX in the hydrogels. The complexation could also reduce the initial burst release effect, and then retard the release of the complexed MTX for a certain period, until the hydrogels started to hydrolytically degrade and all remained MTX was released. Due to the unique structures and properties, the beta-CD-crosslinked gelatin-based hydrogels demonstrated an interesting multiphasic profile for controlled and sustained release of the MTX drug. Thus, the beta-CD-crosslinked gelatin-based hydrogels may be utilized as a promising drug carrier for controlled and sustained release and localized delivery of anticancer drugs.