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

doi:10.3969/j.issn.1006-7795.2015.02.007

首都医科大学学报 ›› 2015, Vol. 36 ›› Issue (2): 192-198.doi: 10.3969/j.issn.1006-7795.2015.02.007

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

魏丽艳, 崔纯莹, 吴建辉, 王玉记

首都医科大学化学生物学与药学院药剂系, 北京 100069

收稿日期:2014-12-08 出版日期:2015-04-21 发布日期:2015-04-16
通讯作者: 王玉记 E-mail:ccmuwyj@126.com
基金资助:
"十二五"重大新药创制科技重大专项(2011ZX09302-007-01)。

Preparation and anti-tumor bioassays of lipid emulsion composed of seal oil as a drug delivery system for docetaxel

Wei Liyan, Cui Chunying, Wu Jianhui, Wang Yuji

School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China

Received:2014-12-08 Online:2015-04-21 Published:2015-04-16
Supported by:
This study was supported by Significant New Drugs Creation "Five-year" Plan Special Science and Technology Major(2011ZX09302-007-01).

摘要/Abstract

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)、pH、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 mV,渗透压在280~320 mOsm·L^-1,0.5012-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。

关键词: 精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-十二烷基脂肪醇, 多西紫杉醇, 脂肪乳, 海豹油, 抗肿瘤

Abstract: 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.

Key words: arginine-glycine-aspartate-phenylalanine-dodecyl alcohols, docetaxel, lipid emulsion, seal oil, anti-tumor

中图分类号:

魏丽艳, 崔纯莹, 吴建辉, 王玉记. 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[J]. 首都医科大学学报, 2015, 36(2): 192-198.

Wei Liyan, Cui Chunying, Wu Jianhui, Wang Yuji. Preparation and anti-tumor bioassays of lipid emulsion composed of seal oil as a drug delivery system for docetaxel[J]. Journal of Capital Medical University, 2015, 36(2): 192-198.

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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

Preparation and anti-tumor bioassays of lipid emulsion composed of seal oil as a drug delivery system for docetaxel

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