Department of Organic Chemistry, UNN Lobachevsky University, Nizhny Novgorod, Russian Federation.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russian Federation.
J Liposome Res. 2024 Sep;34(3):399-410. doi: 10.1080/08982104.2023.2274428. Epub 2023 Nov 1.
Herein, we describe the synthesis of pH-sensitive lipophilic colchicine prodrugs for liposomal bilayer inclusion, as well as preparation and characterization of presumably stealth PEGylated liposomes with above-mentioned prodrugs. These formulations liberate strongly cytotoxic colchicinoid derivatives selectively under slightly acidic tumor-associated conditions, ensuring tumor-targeted delivery of the compounds. The design of the prodrugs is addressed to pH-triggered release of active compounds in the slight acidic media, that corresponds to tumor microenvironment, while keeping sufficient stability of the whole formulation at physiological pH. Correlations between the structure of the conjugates, their hydrolytic stability, colloidal stability, ability of the prodrug retention in the lipid bilayer are described. Several formulations were found promising for further development and in vivo investigations.
在这里，我们描述了 pH 敏感亲脂性秋水仙碱前药的合成，用于脂质体双层包含，以及用上述前药制备和表征假定的隐形 PEG 化脂质体。这些制剂在轻微酸性的肿瘤相关条件下选择性地释放强细胞毒性的秋水仙碱衍生物，确保化合物的肿瘤靶向递送。前药的设计旨在响应 pH 触发在轻微酸性介质中释放活性化合物，该 pH 对应于肿瘤微环境，同时在生理 pH 下保持整个制剂的足够稳定性。描述了缀合物的结构、其水解稳定性、胶体稳定性、前药在脂质双层中保留能力之间的相关性。发现几种制剂具有进一步开发和体内研究的潜力。
