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目的研制淫羊藿苷元(icaritin,IT)脂质体,并对其进行理化性质考察和初步药效学评价。方法采用改进的乙醇注入法制备IT脂质体,考察其形态、粒径及分布、Zeta电位等理化性质;分别采用葡聚糖凝胶柱色谱法、微柱离心法及离心超滤法分离游离药物和脂质体,HPLC测定IT的包封率;以反相透析法考察IT脂质体的体外释放;以包封率为指标,采用正交设计优化制备工艺;采用大鼠骨髓基质细胞模型,初步评价了IT脂质体体外抗骨质疏松作用。结果优化条件下制备的IT脂质体均匀圆整,平均粒径(71.6±6.9)nm,Zeta电位为-(77.3±5.1)mV,采用微柱离心法测得包封率为(91.49±1.15)%,载药量为(9.15±0.22)%,IT脂质体在体外具有一定的缓释性,72h累积释放量大于90%;初步药效学实验表明,IT脂质体能促进骨髓基质细胞向成骨细胞分化,增强成骨细胞活性,抑制骨髓基质细胞向脂肪细胞分化。结论本法制备的IT脂质体粒径小、包封率高,体外细胞实验显示了较好的抗骨质疏松活性,制备方法简单可行,IT脂质体有望开发为抗骨质疏松临床用药剂型。
Objective To develop icaritin (IT) liposomes, and to study its physicochemical properties and preliminary pharmacodynamic evaluation. Methods The liposomes of IT were prepared by modified ethanol injection method. The morphology, particle size and distribution, Zeta potential and other physical and chemical properties were studied. Separation by dextran gel column chromatography, micropillar centrifugation and centrifugal ultrafiltration Drug and liposomes were determined by HPLC. The entrapment efficiency of IT was determined by HPLC. The in vitro release of IT liposomes was investigated by reverse phase dialysis. The encapsulation efficiency was used as an index to optimize the preparation process by orthogonal design. The rat bone marrow stromal cell model , Preliminarily evaluated the anti-osteoporosis effect of IT liposome in vitro. Results The IT liposomes prepared under optimal conditions were uniformly round with an average particle size of 71.6 ± 6.9 nm and a Zeta potential of (77.3 ± 5.1) mV. The encapsulation efficiency was 91.49 ± 1.15 ), Drug loading (9.15 ± 0.22)%, IT liposomes in vitro with a certain degree of sustained release, 72h cumulative release of more than 90%; preliminary pharmacodynamic experiments show that IT liposomes can promote bone marrow stromal cells Differentiate into osteoblasts, enhance osteoblast activity, and inhibit the differentiation of bone marrow stromal cells into adipocytes. Conclusion The liposomes prepared by this method have small particle size and high entrapment efficiency. In vitro cell experiments show good anti-osteoporosis activity. The preparation method is simple and feasible. IT liposomes are expected to be developed as anti-osteoporosis clinical drug Formulation.