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-1,0.50<Ke<0.70,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。
Objective To design arginine-glycine-aspartate-phenylalanine-dodecyl alcohols mediated docetaxel lipid emulsion [ RGDFOC12-DTX-LE] and investigate its anti-tumor activity. Methods DTX a broadly used anti-cancer drug, was tested as the model drug. The RGDFOC12-DTX-LE was made of seal oil, lecithin, RGDFOC12 and glycerol. The formulation was obtained by high pressured homogenization. Results The physicochemical property of RGDFOC12-DTX-LE was evaluated by measuring mean particle size（190 nm^250 nm）, Zeta potential（-30 mV to -40 mV）, eccentricity constants（Ke〈0. 7）, pH（6. 5~8. 0）. Drug entrapment efficiency was greater than 90%. Transmission electron microscopy（ TEM） and scanning electron microscopy（ SEM） indicated that RGDFOC12-DTX-LEs appeared to be homogeneous and spherical particles. The result of dynamic dialysis method demonstrated that the drug was released from the emulsion slowly. Cytotoxicity studies in HepG2, A375, SH-sy5y, HeLa, MCF-7 cell lines were explored and DTX mixed suspension is the positive control. RGDFOC12-DTX-LE for each cell line had obvious time-dependent effect and presents the characteristics of slow releasing. The in vivo anti-tumor activity experiments showed that RGDFOC12-DTX-LE exhibited better anti-tumor activity. Conclusion In this work RGDF-mediated docetaxel lipid emulsion preparation, had a good in vitro stability, lower injection irritation, enhanced compliance, sustained release property and better anti-tumor effect.
出处
《首都医科大学学报》
CAS
北大核心
2015年第2期192-198,共7页
Journal of Capital Medical University
基金
"十二五"重大新药创制科技重大专项(2011ZX09302-007-01)~~
