(lipo)糖肽,替考拉宁自组装胶束作为紫杉烷类纳米载体。

Self-assembled micelles of the (lipo) glycopeptides, teicoplanin, as taxane nanocarriers.

机构信息

Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

出版信息

Nanotechnology. 2021 Aug 27;32(46). doi: 10.1088/1361-6528/ac1979.

Abstract

The use of nanoparticles is one of the strategies currently studied to minimize the toxicity and lack of tissue specificity of many cancer drugs used in chemotherapy. In this research the physicochemical and biological behavior of a novel self-assembled nanostructure of the antibiotic Teicoplanin (Teico) was characterized as a nanocarrier system for solubilizing highly hydrophobic drugs like Paclitaxel (Ptx) in aqueous media. The Teico micelles were loaded with Ptx in DMSO or PEG-400. The interaction between the loaded micelles and Albumin human serum albumin (HSA) was then studied by size exclusion chromatography. Transmission electron microscopy, dynamic light scattering and high-resolution liquid chromatography were also used to characterize the physicochemical and structural properties of the micelles to form the Teico/Ptx and Teico/Ptx/HSA micelles. Cellular uptake of Ptx was evaluated by fluorescent microscopy. Thecytotoxicity of the complexes was studied on Hep-2 tumor cells, by a Crystal Violet assay. Teico cosolvent-free micelles can solubilize up to 20 mg.mlof Ptx dissolved in PEG, increasing four times the solubility of Ptx in water compared to Abraxane, and 20 000 times the intrinsic solubility of Ptx in water. In addition, Teico/Ptx micelles binds spontaneously HSA through hydrophobic interaction. Teico and Teico/HSA micelles as a Ptx transporter does not affect its release or biological activity. Therefore, Teico/Ptx or Teico/Ptx/HSA complexes appear as new alternatives for transporting larger amounts of hydrophobic drugs that offer advantages, turning it an interesting option for further study.

摘要

纳米粒子的应用是目前研究的策略之一,旨在最小化许多用于化疗的癌症药物的毒性和组织特异性缺乏。在这项研究中,新型抗生素替考拉宁(Teico)自组装纳米结构的物理化学和生物学行为被表征为一种纳米载体系统,用于在水介质中增溶高度疏水性药物如紫杉醇(Ptx)。Teico 胶束在 DMSO 或 PEG-400 中负载 Ptx。然后通过尺寸排阻色谱研究负载胶束与人血清白蛋白(HSA)的相互作用。透射电子显微镜、动态光散射和高分辨率液相色谱也用于表征胶束的物理化学和结构特性,以形成 Teico/Ptx 和 Teico/Ptx/HSA 胶束。通过荧光显微镜评估 Ptx 的细胞摄取。通过结晶紫测定法研究了复合物对 Hep-2 肿瘤细胞的细胞毒性。无 Teico 共溶剂胶束可增溶高达 20mg.mlof Ptx 溶解在 PEG 中,与 Abraxane 相比,Ptx 在水中的溶解度增加了四倍,与 Ptx 在水中的固有溶解度相比增加了 20000 倍。此外,Teico/Ptx 胶束通过疏水相互作用自发结合 HSA。Teico 和 Teico/HSA 胶束作为 Ptx 转运体不会影响其释放或生物活性。因此,Teico/Ptx 或 Teico/Ptx/HSA 复合物似乎是输送更多量疏水性药物的新选择,提供了优势,使其成为进一步研究的有趣选择。

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