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首页> 外文期刊>Acta biomaterialia >A novel thermosensitive polymer with pH-dependent degradation for drug delivery.
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A novel thermosensitive polymer with pH-dependent degradation for drug delivery.

机译：一种新型热敏聚合物，具有pH依赖性降解的药物递送。

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A class of thermosensitive biodegradable multiblock copolymers with acid-labile acetal linkages were synthesized from Pluronic triblock copolymers (Pluronic P85 and P104) and di-(ethylene glycol) divinyl ether. The novel polymers were engineered to form thermogels at body temperature and degrade in an acidic environment. The Pluronic-based acid-labile polymers were characterized using nuclear magnetic resonance, gel permeation chromatography and differential scanning calorimetry. In vitro biocompatibility of the synthesized polymers was evaluated using calorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The polymers showed reverse thermogelling behavior in water around body temperature. The sol-gel transition temperatures of the polymers synthesized from Pluronic P85 and P104 were lowered from 70.3 to 30 degrees C and from 68.5 to 26.9 degrees C, respectively, when the synthesized polymers were compared with corresponding Pluronic block copolymers at a concentration of 25wt.%. The hydrophobic dye solubilization confirmed the formation of polymeric micelles in the aqueous solution. The sizes of the multiblock copolymers increased on a rise in temperature, indicating that thermal gelation was mediated by micellar aggregation. The thermally driven hydrogels showed preferential polymer degradation at acidic pH. At pH 5.0 and 6.5, the release of 40kDa fluorescein isothiocyanate-dextran (FITC-dextran) from the thermally formed hydrogels was completed within 2 and 9 days, respectively. However, FITC-dextran was continuously released up to 30 days at neutral pH. The mechanism of FITC-dextran release at pH 5.0 was mainly an acid-catalyzed degradation, whereas both diffusion and pH-dependent degradation resulted in FITC-dextran release at pH 6.5. The novel polymers hold great potential as a pH-sensitive controlled drug delivery system owing to their interesting phase transition behavior and biocompatibility.
机译：通过Pluronic三嵌段共聚物（Pluronic P85和P104）和二（乙二醇）二乙烯基醚合成了一种具有酸不稳定缩醛键的热敏可生物降解的多嵌段共聚物。设计新型聚合物以在体温下形成热凝胶，并在酸性环境中降解。使用核磁共振，凝胶渗透色谱法和差示扫描量热法表征Pluronic酸的酸性不稳定聚合物。使用热量测定3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物测定评价合成聚合物的体外生物相容性。聚合物在水周围的水中显示出反向热凝血行为。当合成的聚合物与浓度为25wt的相应Pluronic嵌段共聚物进行比较时，从Pluronic P85和P104合成的聚合物的溶胶 - 凝胶转变温度分别从70.3至30摄氏度降低到68.5至26.9摄氏度。 ％。疏水性染料溶解证实了在水溶液中形成聚合物胶束。多嵌段共聚物的尺寸在温度升高时增加，表明热凝胶化由胶束聚集介导。热驱动的水凝胶在酸性pH下显示出优先的聚合物降解。在pH 5.0和6.5，分别在2至9天内完成来自热形成的水凝胶的40kda荧光素异硫氰酸酯 - 葡聚糖（FITC-Dextran）的释放。然而，FITC-Dextran在中性pH下连续释放至30天。 FITC-葡聚糖释放在pH5.0下的机制主要是酸催化的降解，而扩散和pH依赖性降解均导致FITC-葡聚糖释放在pH6.5。由于其有趣的相转变行为和生物相容性，新型聚合物具有作为pH敏感的控制药物递送系统的巨大潜力。

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