Combined loading of doxorubicin (DOX) and resveratrol (RSV) in polymeric micelles enabled an increased loading of DOX into a micellar drug delivery system. Herein, we report the coloading of DOX and RSV in amphiphilic diblock copolymer micelles of poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-b-poly(γ-benzyl-ε-caprolactone) (PEG-b-PBCL) for which an increase in the loading efficiency and increased in vitro cytotoxicity was observed. The increased loading was attributed to the favorable interactions of DOX and RSV as well as to the interaction with benzyl substituents of PEG-b-PBCL diblock copolymer micelles. Combination loaded micelles made of PEG-b-PBCL diblock copolymer showed a dramatic improvement in DOX loading in comparison to DOX-only loaded PEG-b-PBCL with an increase in encapsulation efficiency of DOX from 31.0 to 87.7%. Combination loaded micelles also showed increased cytotoxicity to HeLa cells as compared to that of DOX-only loaded micelles. Optimization of the combination loading, size and morphology, drug release, and cellular studies is also reported here. Combination loading was shown to improve the loading capacity and efficiency of both systems and shows promise to improve loading of DOX in polymer micelle systems regardless of the polymer used.

中文翻译：

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阿霉素和白藜芦醇在聚合物胶束中的组合负载可提高负载效率和功效

聚合物胶束中阿霉素（DOX）和白藜芦醇（RSV）的合并加样使胶束药物递送系统中DOX的加样增加。在此，我们报道了在聚乙二醇-b-聚ε-己内酯（PEG- b -PCL）和聚乙二醇-b-聚（γ-观察到苄基-ε-己内酯）（PEG- b - PBCL）的加载效率增加和体外细胞毒性增加。负载的增加归因于DOX和RSV的有利相互作用以及与PEG- b- PBCL二嵌段共聚物胶束的苄基取代基的相互作用。PEG- b制成的复合负载胶束与仅负载DOX的PEG- b -PBCL相比，-PBCL二嵌段共聚物显示出DOX负载的显着改善，DOX的封装效率从31.0提高到87.7％。与仅DOX加载的胶束相比，组合加载的胶束还显示出对HeLa细胞的增强的细胞毒性。此处还报道了组合负载，大小和形态，药物释放和细胞研究的优化。组合负载被证明可以提高两个系统的负载能力和效率，并且显示出有望提高聚合物胶束系统中DOX的负载的能力，而与所使用的聚合物无关。