Department of Applied Molecular Chemistry, College of Industrial Technology, Nihon University, 1-2-1, Izumi-cho, Narashino, Chiba, 275-8575, Japan.
Department of Applied Molecular Chemistry, Graduate School of Industrial Technology, Nihon University, 1-2-1, Izumi-cho, Narashino, Chiba, 275-8575, Japan.
Org Biomol Chem. 2024 Apr 3;22(14):2844-2850. doi: 10.1039/d4ob00216d.
Internal stimuli-responsive controlled release from liposomal vesicles is an innovative approach for site-specific delivery of therapeutic drugs. In this study, to enhance the endosomal pH control of drug release from liposomes, a series of histidine-modified pH-sensitive C-His ( = 8, 12, 18) agents were designed and utilized as triggers for liposomal content release. The pH-dependent properties of C-His-incorporated liposomes were characterized using dynamic light scattering, ζ-potential, and fluorescence spectroscopy. The liposomes maintained a relatively uniform size across all pH conditions. However, the ζ-potential exhibited positive values at endosomal acidic pH levels and neutral or negative values at physiological pH levels. Furthermore, acidic pH-dependent release of both polar content (carboxyfluorescein) and nonpolar content (Nile red) was observed from the C-His-incorporated liposomes. Notably, with C12-His as the pH sensitizer, the pH dependence of liposomal content release was significantly evident. This work establishes endosomal pH-controllable liposome platforms, laying the groundwork for developing clinically applicable triggered release formulations.
从脂质体中进行内部刺激响应控制释放是一种用于治疗药物的靶向递释的创新方法。在这项研究中，为了增强脂质体中药物释放的内体 pH 控制，设计了一系列组氨酸修饰的 pH 敏感的 C-His（=8、12、18）试剂，并将其用作触发脂质体内容物释放的试剂。使用动态光散射、ζ-电位和荧光光谱来表征 C-His 掺入的脂质体的 pH 依赖性。脂质体在所有 pH 条件下保持相对均匀的大小。然而，ζ-电位在内涵体酸性 pH 水平下呈现正值，在生理 pH 水平下呈现中性或负值。此外，从 C-His 掺入的脂质体中观察到极性内容物（羧基荧光素）和非极性内容物（尼罗红）均具有酸性 pH 依赖性释放。值得注意的是，当 C12-His 作为 pH 敏化剂时，脂质体内容物释放的 pH 依赖性非常明显。这项工作建立了可控制的内涵体 pH 的脂质体平台，为开发临床应用的触发释放制剂奠定了基础。
