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

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

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p H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,p H为5.3~6.1,渗透压为820~870 m Osm/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p H环境比血液p H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。

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-DOXLipo-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）.p H 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.p H value and osmotic pressure were in the range of 5.3-6.1 and 820-870 m Osm/kg,respectively.Both PTX and DOX could be encapsulated in liposomes with high encapsulation efficiency（greater than 90%）.Compared with PTX-DOX-Lipo,PTX-DOXLipo-LGC exhibited lower leakage,higher stability in serum and more sustained release profiles.Moreover,a quicker release rate was observed in p H 5.8 PBS compared with p H 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.