N-乙酰半乳糖胺修饰的肝靶向香豆素-6脂质体制备及评价

发布时间：2018-03-26 06:35

  本文选题：去唾液酸糖蛋白受体　切入点：N-乙酰半乳糖胺　出处：《中国新药杂志》2017年16期

【摘要】：目的:本研究采用酶促法构建N-乙酰半乳糖胺(N-acetylgalactosamine,Gal NAc)修饰的脂质体作为荧光标记物-香豆素-6的载体,对其修饰的脂质体理化性质进行评价。方法:采用酶催化法偶联合成Gal NAc-C8-Chol,利用MS,NMR对其结构进行表征,并以此作为导向性材料,采用薄膜分散-挤出法制备载香豆素-6的Gal NAc修饰肝靶向脂质体(NGAL-LP),并对脂质体的包封率、粒径、Zeta电位、体外释放度及RCA120体外结合效率等性质进行了考察。结果:合成的Gal NAc-C8-Chol经MS,NMR鉴定为目标产物。与普通香豆素-6脂质体(LP)相比,本研究所制备的主动肝靶向脂质体(NGAL-LP)的粒径、Zeta电位、包封率、体外释放等理化性质无显著差异,包封率≥98%,平均粒径为(86.74±1.7)nm,平均Zeta电位为(-51.47±0.9)m V。体外释放结果表明,36 h内香豆素-6脂质体在PBS和血浆中的累积释放率8%。RCA120凝集实验表明,只有Gal NAc-C8-Chol修饰的脂质体可经RCA120诱导产生凝集效应。结论:采用酶促法成功构建了Gal NAc修饰的香豆素-6肝靶向脂质体,以期望显著提高体内肝肿瘤的靶向治疗效果。
[Abstract]:Aim: to construct N-acetylgalactosamine- Gal NAc-modified liposome by enzymatic method as the carrier of coumarin -6 as a fluorescent marker. Methods: Gal NAc-C8-Cholwas synthesized by enzymatic coupling method, and its structure was characterized by MS NMR. Gal NAc loaded coumarin -6 was prepared by thin-film dispersion-extrusion method to modify liposome NGAL-LPN. The encapsulation efficiency and particle size of liposome were determined. The in vitro release and in vitro binding efficiency of RCA120 were investigated. Results: the synthesized Gal NAc-C8-Chol was identified as the target product by MS NMR. Compared with the conventional coumarin -6 liposome, the active liposome (NGAL-LPN) prepared in this study was characterized by its particle size and Zeta potential. There was no significant difference in entrapment efficiency and in vitro release. The entrapment efficiency was 鈮，

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