The natural bioactive compound caffeic acid phenethyl ester (CAPE) possesses antioxidant, antiinflammatory and anticancer activity. However, the in vivo application of CAPE is limited due to its poor solubility in aqueous media. In this contribution, we report a strategy for enhancing the solubility of CAPE in water by novel micellar carriers comprising segments structurally similar to the CAPE molecule. A series of amphiphilic poly(ethylene oxide)- b -poly(α-cinnamyl-ε-caprolactone- co -ε-caprolactone)- b -poly(ethylene oxide) (PEO- b -P(CyCL- co -CL)- b -PEO) triblock copolymers were synthesized by combining ring-opening copolymerization and “click” reactions. Calculations of the Flory–Huggins parameter suggested that P(CyCL- co -CL) copolymers have a higher affinity for CAPE than do PCL polymer. Micellar carriers based on PEO- b -P(CyCL- co -CL)- b -PEO were formed via the solvent evaporation method and then loaded with CAPE. Dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM) revealed the formation of nanosized spherical micelles that maintained their structural integrity upon dilution to 0.055–0.06 g L −1 . The main characteristics of the PEO- b -P(CyCL- co -CL)- b -PEO systems were compared to those of the PEO- b -PCL- b -PEO system. The attachment of pendant cinnamyl moieties to the hydrophobic PCL block enhanced the encapsulation efficiency of the micelles and reduced their burst release behavior. Polymeric micelles based on amphiphilic poly(ethylene oxide)- b -poly( ε -caprolactone)- b -poly(ethylene oxide)(PEO- b -PCL- b -PEO) triblock copolymers improved the solubility of caffeic acid phenethyl ester (CAPE) in aqueous media. Further on, the grafting of pendant cinnamyl moieties to the PCL block enhanced the compatibility between CAPE and the micellar core, thus increasing the encapsulation efficiency and reducing the burst release effect as compared to those of micelles with an unmodified PCL core.

中文翻译：

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带有肉桂基侧基的功能性嵌段共聚物，用于增强咖啡酸苯乙酯的增溶

天然生物活性化合物咖啡酸苯乙酯（CAPE）具有抗氧化、抗炎和抗癌活性。然而，由于CAPE在水性介质中的溶解性差，其在体内的应用受到限制。在这项贡献中，我们报告了一种通过新型胶束载体提高 CAPE 在水中溶解度的策略，该胶束载体包含结构类似于 CAPE 分子的片段。一系列两亲性聚(环氧乙烷)-b-聚(α-肉桂基-ε-己内酯-co-ε-己内酯)-b-聚(环氧乙烷)(PEO-b-P(CyCL-co-CL)- b -PEO) 三嵌段共聚物是通过结合开环共聚和“点击”反应合成的。Flory-Huggins 参数的计算表明 P(CyCL-co-CL) 共聚物对 CAPE 的亲和力高于 PCL 聚合物。通过溶剂蒸发法形成基于PEO-b-P(CyCL-co-CL)-b-PEO的胶束载体，然后负载CAPE。动态光散射 (DLS) 和低温透射电子显微镜 (cryo-TEM) 揭示了纳米尺寸球形胶束的形成，在稀释至 0.055–0.06 g L -1 时保持其结构完整性。将PEO-b-P(CyCL-co-CL)-b-PEO系统的主要特征与PEO-b-PCL-b-PEO系统的主要特征进行比较。悬垂的肉桂基部分与疏水性 PCL 嵌段的连接提高了胶束的封装效率并降低了它们的突释行为。基于两亲性聚（环氧乙烷）- b -聚（ε -己内酯）- b -聚（环氧乙烷）（PEO- b -PCL- b -PEO）三嵌段共聚物的聚合物胶束提高了咖啡酸苯乙酯（CAPE）的溶解度) 在水介质中。此外，与未修饰的 PCL 核的胶束相比，将肉桂基侧基部分接枝到 PCL 嵌段上增强了 CAPE 与胶束核之间的相容性，从而提高了包封效率并降低了突释效应。