以海豹油为基质的多西紫杉醇脂肪乳的制备及其抗肿瘤活性研究

发布时间：2019-06-22 13:42

【摘要】：目的制备精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-十二烷基脂肪醇(arginine-glycine-aspartate-phenylalanine-dodecyl alcohols,RGDFOC12)介导的多西紫杉醇(docetaxel,DTX)脂肪乳简称RGDFOC12-DTX脂肪乳,并考察其抗肿瘤活性。方法以抗肿瘤药物DTX为模型药物,以海豹油为油相,卵磷脂为乳化剂,两亲性RGDFOC12为新型膜材,通过高压乳匀法制备RGDFOC12-DTX脂肪乳。并考察其粒径、Zeta电位、渗透压、离心率(Ke)、p H、包封率、体外释药行为和抗肿瘤作用效果。结果 RGDFOC12-DTX脂肪乳粒径在190~250 nm,Zeta电位在-30~-40 m V,渗透压在280~320 m Osm·L-1,0.50Ke0.70,p H在6.5~8.0,载药质量浓度为1 000 mg/L,包封率在90%以上。电镜下观察RGDFOC12-DTX脂肪乳粒子呈均匀球形。体外释放实验显示RGDFOC12-DTX脂肪乳呈缓释的特点,体外抗肿瘤活性实验显示,RGDFOC12-DTX脂肪乳对各细胞系有明显的时间依赖效应,且呈现出缓释的特点。体内抗肿瘤活性实验显示,RGDFOC12-DTX脂肪乳具有更好的抗肿瘤活性。结论本文报道了RGDFOC12-DTX脂肪乳的新剂型及制备方法,该剂型可有效增加药物的稳定性,降低注射时的刺激性,增强机体依从性且具有缓释性和更好的抗肿瘤活性。
[Abstract]:Objective to prepare arginine-glycine-aspartic acid-phenylalanine-lauryl fatty alcohol (arginine-glycine-aspartate-phenylalanine-dodecyl alcohols,RGDFOC12)-mediated docetaxel (docetaxel,DTX) fat emulsion for short RGDFOC12-DTX fat emulsion and to investigate its antitumor activity. Methods RGDFOC12-DTX fat emulsion was prepared by high pressure emulsion homogenization with DTX as model drug, seal oil as oil phase, lecithin as emulsifier and Amphiphilic RGDFOC12 as new membrane material. The particle size, Zeta potential, osmotic pressure, eccentricity (Ke), p H, entrapment efficiency, drug release behavior in vitro and antitumor effect were also investigated. Results the particle size of RGDFOC12-DTX fat milk was 190 脳 250 nm,Zeta potential at-30 Osm 路L-1, osmotic pressure was 280? 320 m Osm 路L-1, osmotic pressure was 0.50 Ke0.70, pH was 6.5? 8.0. the entrapment efficiency of 1000 mg/L, was over 90%. Under electron microscope, RGDFOC12-DTX fat emulsion particles were uniformly spherical. In vitro release test showed that RGDFOC12-DTX fat emulsion showed sustained release. In vitro antitumor activity test showed that RGDFOC12-DTX fat emulsion had obvious time-dependent effect on each cell line and showed sustained release. In vivo antitumor activity test showed that RGDFOC12-DTX fat emulsion had better antitumor activity. Conclusion A new dosage form and preparation method of RGDFOC12-DTX fat emulsion are reported in this paper. the dosage form can effectively increase the stability of the drug, reduce the irritation during injection, enhance the compliance of the body, and has sustained release and better antitumor activity.
【作者单位】：首都医科大学化学生物学与药学院药剂系;
【基金】：“十二五”重大新药创制科技重大专项(2011ZX09302-007-01)~~
【分类号】：R943;R96

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