Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels.
Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels.
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自组装可生物降解热敏水凝胶中的大分子扩散。
DOI：
10.1021/ma902186e
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发表时间：
2010
期刊：
影响因子：
5.5
通讯作者：
Siegel,RonaldA
中科院分区：
文献类型：
--
作者：
Vermonden,Tina;Jena,SidharthaS;Barriet,David;Censi,Roberta;vanderGucht,Jasper;Hennink,WimE;Siegel,RonaldA
由温度变化引发的水凝胶形成是一种吸引人的机制，可用于药物应用中的生物材料，如治疗蛋白的输送。本研究以温敏性聚(N-(2-羟丙基)甲基丙烯酰胺乳酸酯)为侧翼的ABA三嵌段聚合物和亲水性聚乙二醇B-嵌段为原料制备了水凝胶。合成了固定长度A嵌段(∼22 kDa)、不同PEG中嵌段长度(2 kDa、4 kDa和10 kDa)的聚合物，并将其溶解在稀释异硫氰酸酯标记的葡聚糖(70 kDa和500 kDa)的水中。通过提高温度，形成了包埋右旋糖苷的水凝胶。光漂白后的荧光恢复(FRAP)研究表明，温度高于25℃时，葡聚糖染料的扩散系数和可移动分数随温度升高而降低。激光共聚焦扫描显微镜和低温扫描电子显微镜表明，凝胶结构依赖于聚乙二醇嵌段长度。与聚乙二醇大嵌段的聚合物相比，聚乙二醇小嵌段的聚合物在更大程度上发生了相分离，形成富聚合物和富水的区域。通过改变聚乙二醇链的长度，从而改变凝胶的结构，可以定制FITC-葡聚糖的迁移率。在生理pH下，随着时间的推移，水凝胶会因酯类的水解而降解，导致包裹的染料的流动性增加。由于扩散可以根据聚合物的设计和浓度以及温度进行控制，因此这些生物相容水凝胶是具有潜在潜力的生物可降解材料，可用于大分子药物输送。
Hydrogel formation triggered by a change in temperature is an attractive mechanism forin situgelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl)methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A-blocks (∼22 kDa) but differing PEG-midblock lengths (2, 4, and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDa). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, the mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potentialin situgelling biodegradable materials for macromolecular drug delivery.