Docetaxel (DTX) is one of the most promising chemotherapeutic agents for a variety of solid tumors. However, the clinical efficacy of the marketed formulation, Taxotere®, is limited due to its poor aqueous solubility, side effects caused by the emulsifier, and low selective DTX distribution in vivo. Here a facile, well-defined, and easy-to-scale up DTX-loaded N-(tert-butoxycarbonyl)-L-phenylalanine end-capped methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-b-PLA-Phe(Boc)) micelles (DTX-PMs) were prepared in an effort to develop a less toxic and more efficacious docetaxel formulation. The physicochemical properties, pharmacokinetics, biodistribution, and in vivo anti-tumor efficacy were evaluated in comparison to the marketed DTX formulation Taxotere®. DTX was successfully encapsulated in the hydrophobic micellar core with a high encapsulation efficiency (> 95%) and a high drug loading capacity (4.81 ± 0.08%). DTX-PMs exhibited outstanding stability in the aqueous environment due to the strong interactions between the terminal amino acid residues and docetaxel. The pharmacokinetic study in Sprague-Dawley rats revealed higher DTX concentrations in both whole blood and plasma for the group treated with DTX-PMs than that treated with Taxotere® due to the improved stability of the micellar formulation. In human non-small cell lung cancer (A549) tumor-bearing Balb/c nude mice, DTX-PMs significantly improved DTX accumulation and stalled DTX elimination in tumors than in bone marrow. Furthermore, only by half of the DTX dosage, our DTX/mPEG-b-PLA-Phe(Boc) micelles can achieve similar therapeutic effects as Taxotere®. Altogether, DTX-PMs hold great promise as a simple and effective drug delivery system for cancer chemotherapy.

中文翻译：

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药物相互作用mPEG-b-PLA-Phe（Boc）胶束增强了多西紫杉醇的耐受性和抗肿瘤功效。

多西他赛（DTX）是用于多种实体瘤的最有前途的化学治疗剂之一。然而，由于其水溶性差，乳化剂引起的副作用以及体内低选择性DTX分布，市售制剂Taxotere®的临床疗效受到限制。这是一种简便，定义明确且易于按比例放大的DTX负载的N-（叔丁氧基羰基）-L-苯丙氨酸封端的甲氧基-聚（乙二醇）-嵌段-聚（D，L-丙交酯） （mPEG-b-PLA-Phe（Boc））胶束（DTX-PMs）的制备旨在开发毒性更小，更有效的多西他赛制剂。与市售DTX制剂比较，评估了其理化性质，药代动力学，生物分布和体内抗肿瘤功效。DTX以高的包封率（> 95％）和高的载药量（4.81±0.08％）成功地包封在疏水性胶束芯中。由于末端氨基酸残基和多西他赛之间的强相互作用，DTX-PM在水性环境中表现出出色的稳定性。在Sprague-Dawley大鼠中进行的药代动力学研究表明，由于胶束制剂的稳定性提高，DTX-PMs治疗组的全血和血浆DTX浓度均高于Taxotere®治疗组。在人类非小细胞肺癌（A549）荷瘤Balb / c裸鼠中，与骨髓相比，DTX-PMs显着改善了肿瘤中DTX的积累并阻止了DTX的消除。此外，仅DTX剂量的一半，我们的DTX / mPEG-b-PLA-Phe（Boc）胶束可达到与Taxotere®类似的治疗效果。总而言之，DTX-PM作为癌症化疗的简单有效的药物递送系统具有广阔的前景。