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多糖锚定修饰紫杉醇-阿霉素复方脂质体的制备及体外评价

郝静梅, 王卉, 李琼, 朱靓, 张勇, 霍美蓉

郝静梅, 王卉, 李琼, 朱靓, 张勇, 霍美蓉. 多糖锚定修饰紫杉醇-阿霉素复方脂质体的制备及体外评价[J]. 中国药科大学学报, 2017, 48(6): 680-686. DOI: 10.11665/j.issn.1000-5048.20170608
引用本文: 郝静梅, 王卉, 李琼, 朱靓, 张勇, 霍美蓉. 多糖锚定修饰紫杉醇-阿霉素复方脂质体的制备及体外评价[J]. 中国药科大学学报, 2017, 48(6): 680-686. DOI: 10.11665/j.issn.1000-5048.20170608
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HAO Jingmei, WANG Hui, LI Qiong, ZHU Liang, ZHANG Yong, HUO Meirong. Preparation and in vitro studies of polysaccharide modified compound liposomes loaded with paclitaxel and doxorubicin[J]. Journal of China Pharmaceutical University, 2017, 48(6): 680-686. DOI: 10.11665/j.issn.1000-5048.20170608
Citation: HAO Jingmei, WANG Hui, LI Qiong, ZHU Liang, ZHANG Yong, HUO Meirong. Preparation and in vitro studies of polysaccharide modified compound liposomes loaded with paclitaxel and doxorubicin[J]. Journal of China Pharmaceutical University, 2017, 48(6): 680-686. DOI: 10.11665/j.issn.1000-5048.20170608
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多糖锚定修饰紫杉醇-阿霉素复方脂质体的制备及体外评价

  • 1.

    中国药科大学制药有限公司

  • 2.

    中国药科大学天然药物活性组分与药效国家重点实验室

Preparation and in vitro studies of polysaccharide modified compound liposomes loaded with paclitaxel and doxorubicin

摘要

    摘要
  • 摘要: 采用薄膜分散-硫酸铵梯度法制备了紫杉醇-阿霉素复方脂质体，并以N-十二烷基-O-羟乙基两亲性壳聚糖衍生物锚定修饰，透射电镜观察脂质体形态，动态光散射法测定粒径及表面电荷，数字酸度计及渗透压测定仪检测其pH及渗透压，HPLC法测定并计算两种药物包封率、渗漏稳定性、血浆稳定性及体外释放行为。所制备的多糖锚定修饰复方脂质体呈球形，粒径分布均匀，在150 nm左右，pH为5.3~6.1，渗透压为820~870 mOsm/kg，对两种药物皆具有较高的包封率(均大于90%)，且和非多糖锚定修饰脂质体相比，药物泄漏率显著降低，血浆稳定性显著提高，缓释能力增强，且在肿瘤模拟pH环境比血液pH环境具有更快的释药速度。本研究制备的多糖修饰复方脂质体具有优良的药物负载、稳定性及缓释能力，在临床联合化疗具有一定的应用前景。
    Abstract: The objectives of this study were to prepare polysaccharide modified compound liposomes loaded with paclitaxel(PTX)and doxorubicin(DOX)and characterize their phyisicochemical properties, stability and in vitro release profiles. Both PTX-DOX-Lipo and N-lauryl-O-glycol chitosan(LGC)modified liposomes(PTX-DOX-Lipo-LGC)were successfully prepared, and the morphology of the liposomes was observed by transmission electron microscope(TEM), and particle size and zeta potential were analyzed by dynamic light scattering(DLS). pH and osmotic pressure were also determined. The drug loading and encapsulation efficiency, stability and in vitro release were assayed using high-performance liquid phase. Both PTX-DOX-Lipo and PTX-DOX-Lipo-LGC exhibited spherical shape with smooth surface. The average diameter was about 150 nm. pH value and osmotic pressure were in the range of 5. 3-6. 1 and 820-870 mOsm/kg, respectively. Both PTX and DOX could be encapsulated in liposomes with high encapsulation efficiency(greater than 90%). Compared with PTX-DOX-Lipo, PTX-DOX-Lipo-LGC exhibited lower leakage, higher stability in serum and more sustained release profiles. Moreover, a quicker release rate was observed in pH 5. 8 PBS compared with pH 7. 4 PBS. PTX-DOX-Lipo-LGC with high drug loading, good stability and sustained drug release profiles has a wide prospect in future clinical application.
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  • 刊出日期:  2017-12-24

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