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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。
OBJECTIVE: In this study, liposomes modified with N-acetylgalactosamine (GalNAc) were constructed by enzymatic method as a fluorescent label-coumarin-6 vector. The physical and chemical properties of the modified liposomes Evaluation. Methods: GalNAc-C8-Chol was synthesized by enzyme-catalyzed coupling. The structure was characterized by MS and NMR. The structure of GalNAc-C8-Chol was characterized by means of membrane dispersion-extrusion NAc modified liver targeting liposomes (NGAL-LP), and liposome encapsulation efficiency, particle size, Zeta potential, in vitro release and RCA120 in vitro binding efficiency and other properties were investigated. Results: The synthesized GalNAc-C8-Chol was identified by MS and NMR as the target product. Compared with normal coumarin-6 liposomes (LP), the particle size, zeta potential, entrapment efficiency and in vitro release of active liver targeting liposomes (NGAL-LP) The encapsulation efficiency was ≥98%, the average particle diameter was (86.74 ± 1.7) nm and the average zeta potential was (-51.47 ± 0.9) mV. In vitro release results showed that the cumulative release rate of coumarin-6 liposomes in PBS and plasma within 36 h was <8%. The RCA120 agglutination test showed that only Gal NAc-C8-Chol modified liposomes can induce agglutination by RCA120. CONCLUSION: GalNAc-modified coumarin-6 liver-targeted liposomes were successfully constructed by enzymatic method in order to significantly improve the targeted therapeutic effect of hepatic tumors in vivo.