通过脂酶A2活性从DPPC脂质体释放素:胆固醇和两性共聚物的作用
Marco Soto-Arriaza1, Eduardo Cena Ahumada2, Sebastián Bonardd3,4
1Escuela de Química y Farmacia, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.
Journal of liposome research
|June 8, 2024
概括
两性共聚合物和胆固醇调节双基酸胆 (DPPC) 脂质体稳定性和素释放. 低度的共聚合物增强了脂质体的设计,在HEK-293细胞中显示出低细胞毒性.
科学领域:
- 基于脂质的药物输送系统
- 纳米技术在医学中的应用
- 生物材料科学是生物材料的科学.
背景情况:
- 双基酸胆 (DPPC) 脂质体被广泛研究用于药物输送.
- 从脂质体中控制封装分子的释放对于治疗疗效至关重要.
- 众所周知,两性共聚物和胆固醇会影响脂质体的特性.
研究的目的:
- 评估两性共聚物和胆固醇对DPPC脂质体稳定性的影响.
- 为了研究通过脂酶A2 (PLA2) 调节DPPC脂质体释放素的调节.
- 在基于细胞的测试中评估修饰DPPC脂质体的细胞毒性.
主要方法:
- 在DPPC脂质体中纳入双阻断和三阻断的两性共聚物和胆固醇.
- 在不同的条件下测量从脂质体中释放的素.
- 在HEK-293和HeLa细胞中评估脂质体介导的细胞毒性.
- 用外源性PLA2和离子进行的酶活性测定.
主要成果:
- 在低度的共聚合物中,素的释放量减少,并且与高度的对照剂相似.
- 结合胆固醇降低了PLA2介导的素释放,最大效果在18-20mol%之间.
- DPPC脂质体显示出低细胞毒性;然而,含胆固醇和共聚物的配方表现出剂量依赖的细胞毒性.
结论:
- 低度的两性共聚物可以用于设计新型DPPC脂质体.
- 胆固醇和共聚物有效调节脂质体稳定和药物释放动力学.
- 开发的脂质体配方在HEK-293细胞中表现出低细胞毒性,素的释放取决于PLA2活性和离子.
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