Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Zabrze, Poland.
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland.
J Biomed Mater Res B Appl Biomater. 2024 Jan;112(1):e35318. doi: 10.1002/jbm.b.35318. Epub 2023 Aug 31.
The interest in combining chemosensitizers with cytostatics in cancer therapy is growing, which causes also a need to develop their delivery systems. Example of the combination with beneficial therapeutic effects is docetaxel (Dtx) and resveratrol (Res). Although poly(lactide)-co-poly(ethylene glycol) (PLA-PEG) micelles have been considered as one of the most promising platforms for drug delivery, their properties may depend on the stereoisomeric form of hydrophobic block. Therefore, the aim of this study was evaluation of the effect of PLA block on co-encapsulation and release rate of Dtx and Res, which has not been studied so far. This article presents a comparison of single- (Dtx or Res) and dual-drug (Dtx and Res) loaded micelles obtained from poly(l,l-lactide)-co-poly(ethylene glycol) (PLLA-PEG) and poly(d,l-lactide)-co-poly(ethylene glycol) (PDLLA-PEG). The analyzes of the micelles have been conducted including morphology, drug(s) encapsulation efficiency, intermolecular interactions, in vitro drug release, and cytotoxicity. Differences in drug loading ability and release profile have been observed between Res and Dtx but also depending on the polymer and number of drugs in micelles (single vs. dual loaded). The PLLA-PEG micelles have a significantly higher Dtx encapsulation capacity than PDLLA-PEG micelles. The highest cytotoxicity was shown for Dtx and Res dual-loaded micelles, regardless of the polymer. The findings may be used for selection of PLA-based drug delivery systems containing Dtx and Res.
将化学增敏剂与细胞抑制剂联合用于癌症治疗的兴趣日益浓厚，这也促使人们开发其输送系统。与有益治疗效果相结合的一个例子是多西紫杉醇（Dtx）和白藜芦醇（Res）。尽管聚（乳酸）-共-聚（乙二醇）（PLA-PEG）胶束已被认为是最有前途的药物输送平台之一，但它们的性质可能取决于疏水性嵌段的立体异构体形式。因此，本研究的目的是评估 PLA 嵌段对 Dtx 和 Res 共包封和释放速率的影响，迄今为止尚未对此进行研究。本文比较了由聚（L-丙交酯）-共-聚（乙二醇）（PLLA-PEG）和聚（D,L-丙交酯）-共-聚（乙二醇）（PDLLA-PEG）获得的单药（Dtx 或 Res）和双药（Dtx 和 Res）载药胶束。对胶束进行了形态、药物（s）包封效率、分子间相互作用、体外药物释放和细胞毒性分析。在 Res 和 Dtx 之间观察到药物负载能力和释放特性的差异，但也取决于聚合物和胶束中的药物数量（单载 vs. 双载）。PLLA-PEG 胶束对 Dtx 的包封能力明显高于 PDLLA-PEG 胶束。无论聚合物如何，Dtx 和 Res 双载胶束的细胞毒性最高。研究结果可用于选择包含 Dtx 和 Res 的 PLA 基药物输送系统。
