Nano-vesicles of multi-tailed macrocycle molecules have demonstrated a great ability to enhance the bioavailability of hydrophobic drugs. In this study, amphiphilic multi-tailed resorcinarene (MTR) derivative was synthesised in two steps reaction by O-alkylation of 4-hydroxybenzaldehyde and then condensation with resorcinol. The synthesised amphiphilic macrocycle was characterized by 1 H-NMR, FT-IR and mass spectrometry. Self-assembly and aggregation behaviour of amphiphilic macrocycle was studied in aqueous medium and vesicles were characterised for morphology, critical micelle concentration (CMC), size and surface potential and cellular biocompatibility. The self-assembling ability of MTR was used for one-step loading of hydrophobic drug, i.e. clarithromycin. MTR presented a low CMC value, i.e. 0.055 mM and formed niosomal vesicles with a mean diameter of 210 ± 2 nm, narrow size distribution and 65.12 ± 3.31% drug entrapment efficiency. MTR vesicles showed sustained in vitro drug release while maximum drug release was achieved at 8 h. Biocompatibility of MTR was investigated with blood haemolysis and cytotoxicity assays. The results indicated suitability of MRT as amphiphilic macromolecular surfactant. Graphical abstract

中文翻译：

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自组装多尾间苯二酚基超分子两亲物的合成及生物相容性

多尾大环分子的纳米囊泡已证明具有增强疏水性药物生物利用度的强大能力。在这项研究中，通过 4-羟基苯甲醛的 O-烷基化，然后与间苯二酚缩合，通过两步反应合成了两性多尾间苯二酚 (MTR) 衍生物。合成的两亲性大环化合物通过 1 H-NMR、FT-IR 和质谱进行了表征。在水性介质中研究了两亲性大环化合物的自组装和聚集行为，并对囊泡的形态、临界胶束浓度 (CMC)、大小和表面电位以及细胞生物相容性进行了表征。MTR的自组装能力用于一步加载疏水性药物，即克拉霉素。MTR 呈现低 CMC 值，即 0。055 mM 并形成平均直径为 210 ± 2 nm、窄尺寸分布和 65.12 ± 3.31% 药物包封率的 niosomal 囊泡。MTR 囊泡表现出持续的体外药物释放，而在 8 小时时达到最大药物释放。用血液溶血和细胞毒性试验研究了 MTR 的生物相容性。结果表明 MRT 适合作为两亲性大分子表面活性剂。图形概要