Abstract This study presents a new groundbreaking methodology for integrating innovative concepts to develop novel drug-delivery strategies. This methodology combines genetically engineered elastin-like recombinamers (ELRs) with supercritical fluid (SCF) techniques to encapsulate a poorly water-soluble drug in a one-step process. The chemotherapeutic agent docetaxel (DTX) is encapsulated with a block copolymer ELR containing the RGD peptide, a specific target sequence for cancer cells, using the supercritical anti-solvent (SAS) technique in a high process yield of up to 70%. SEM studies show spherical microparticles of 10 μm after encapsulation. After dispersion under physiological conditions, microparticles disaggregate into stable monodisperse nanoparticles of 40 nm size and −30 mV ζ-potential. This protects the drug, as confirmed by NMR analysis, thereby increasing the water solubility of DTX up to fifty orders of magnitude. The delivery process is governed by the Fick diffusion mechanism and indicates that the presence of DTX on the particles surface is practically negligible. Cellular assays showed that, due to the presence of the cancer target sequence RGD, breast cancer cells were more affected than human endothelial cells, thus meaning that the strategy developed in this work opens the way to new controlled release systems more precise than non-selective chemotherapeutic drugs.

中文翻译：

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使用超临界反溶剂工艺生产用于多西紫杉醇包封的弹性蛋白样重组体纳米颗粒并用作智能药物输送系统

摘要 本研究提出了一种新的开创性方法，用于整合创新概念以开发新的药物递送策略。该方法将基因工程弹性蛋白样重组体 (ELR) 与超临界流体 (SCF) 技术相结合，以一步法封装水溶性差的药物。化疗剂多西紫杉醇 (DTX) 被包含 RGD 肽的嵌段共聚物 ELR 封装，RGD 肽是癌细胞的特定靶序列，使用超临界反溶剂 (SAS) 技术以高达 70% 的高工艺收率。SEM 研究显示封装后为 10 μm 的球形微粒。在生理条件下分散后，微粒分解为 40 nm 大小和 -30 mV ζ 电位的稳定单分散纳米粒子。这样可以保护药物，NMR 分析证实，从而将 DTX 的水溶性增加到 50 个数量级。传递过程受 Fick 扩散机制控制，表明颗粒表面上 DTX 的存在实际上可以忽略不计。细胞分析表明，由于癌症靶序列 RGD 的存在，乳腺癌细胞比人内皮细胞受到的影响更大，这意味着这项工作中开发的策略为比非选择性更精确的新控释系统开辟了道路化疗药物。