Martinez Espinoza Maria Isabel, Gül Sezen, Mugnaini Luisa, Cellesi Francesco
Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy.
Molecules. 2024 Nov 21;29(23):5511. doi: 10.3390/molecules29235511.
A thermoresponsive copolymer based on oligo(ethylene glycol) methacrylate, Chol-P(MEOMA-co-OEGMA), was synthesized using Atom Transfer Radical Polymerization (ATRP) and incorporated into thermosensitive liposomes (TSLs) for controlled drug release. The copolymer exhibited a lower critical solution temperature (LCST) of 37 °C, making it suitable for biomedical applications requiring precise thermal triggers. The copolymer was incorporated into various TSL formulations alongside phospholipids such as DPPC, Lyso-PC, HSPC, and DSPC. Physicochemical characterization of the liposomes, including average size, polydispersity index, loading efficiency (LE), and encapsulation efficiency (EE), was performed using dynamic light scattering and fluorescence spectroscopy. The results showed that the incorporation of the copolymer slightly affected particle size and decreased LE and EE in most formulations. Lyso-PC-containing formulations exhibited lower LE and EE, likely due to instability during purification. Albumin encapsulation demonstrated lower LE compared to the smaller carboxyfluorescein drug model, highlighting the influence of molecular weight on loading. Although copolymer-modified liposomes showed reduced loading capacity, they enhanced thermoresponsiveness in HSPC-based formulations. These findings suggest that incorporating thermoresponsive polymers into TSLs can optimize drug delivery systems for targeted, thermally triggered release.
通过原子转移自由基聚合（ATRP）合成了一种基于甲基丙烯酸寡聚乙二醇酯的温敏共聚物Chol-P(MEOMA-co-OEGMA)，并将其掺入热敏脂质体（TSL）中以实现药物的控释。该共聚物的低临界溶液温度（LCST）为37°C，使其适用于需要精确热触发的生物医学应用。该共聚物与磷脂（如DPPC、溶血磷脂酰胆碱、氢化大豆磷脂酰胆碱和二硬脂酰磷脂酰胆碱）一起掺入各种TSL制剂中。使用动态光散射和荧光光谱对脂质体进行了物理化学表征，包括平均粒径、多分散指数、负载效率（LE）和包封效率（EE）。结果表明，共聚物的掺入对粒径有轻微影响，并且在大多数制剂中降低了LE和EE。含溶血磷脂酰胆碱的制剂表现出较低的LE和EE，这可能是由于纯化过程中的不稳定性。与较小的羧基荧光素药物模型相比，白蛋白包封显示出较低的LE，突出了分子量对负载的影响。尽管共聚物修饰的脂质体显示出负载能力降低，但它们增强了基于氢化大豆磷脂酰胆碱的制剂的热响应性。这些发现表明，将温敏聚合物掺入TSL中可以优化药物递送系统，以实现靶向、热触发释放。
