红细胞膜包裹PLGA纳米粒的制备和体外毒性及药物释放初探

Preparation of erythrocyte membrane-camouflaged PLGA nanoparticles and preliminary investigation on their cytotoxicity and drug release in vitro

目的:制备红细胞膜包裹PLGA纳米粒(RBC-NP)并进行结构表征、稳定性及体外毒性和药物释放的探究。方法:纳米沉淀法制备PLGA纳米粒(PLGA NP);脂质体挤压法制备红细胞膜和RBC-NP;Malvern ZS90测定粒径和分散系数;透射电镜(TEM)观察RBC-NP的形态。将DiOC18(3)载入RBC-NP和PLGA NP,探究二者的药物体外释放特性。采用CCK8法检测细胞的相对增殖率,比较RBC-NP与PLGA NP的细胞毒性。结果:RBC-NP与PLGA NP的粒径之差为11.1~14.2 nm,分散系数在0.131~0.155。TEM显示RBC-NP呈壳-核结构,核心为PLGA,外包裹单层红细胞膜。RBC-NP在PBS和超纯水中6 d内均保持稳定。RBC-NP具有良好体外缓释作用。0.25,0.5,1 mg·m L^(-1)3组中,RBC-NP的细胞相对增殖率均显著性高于PLGA NP(P<0.01)。结论:具有壳-核结构的RBC-NP已被成功制备,具有药物缓释作用且体外毒性显著降低。

Objective： To prepare the erythrocyte membrane-camouflaged PLGA nanoparticles （RBC-NP）,and to investigate their stability,drug release ability and cytotoxicity.Methods： RBC-NP and PLGA nanoparticles （PLGA NP） were prepared by nanoprecipitation and extrusion.The nanoparticles were characterized by Malvern ZS90 and transmission electron microscopy.DiO was loaded into two carriers,and their release characters in vitro were studied.CCK8 kit assay was used to detect the cell proliferation rates.Cytotoxicity of RBC-NP and PLGA NP was determined and compared.Results： The differences in particle size of three groups of RBC-NP and PLGA NP were 11.1 ~ 14.2 nm,and PDI scale of particles in different groups ranged from 0.131 to 0.155.Transmission electron microscopic pictures showed that the RBC-NPs had clear core-shell structure.The RBC-NP was stable in double distilled water or PBS for 6 days.RBC-NP showed a sustained release property compared to PLGA NP.The cytotoxicity of RBC-NP was significant lower than that of PLGA NP at 0.25,0.5 and 1 mg·m L^（-1）.Conclusion：RBC-NPs have been prepared successfully,and shown lower cytotoxicity and sustained release ability in vitro.