李 翔, 张 婧, 王东凯, 潘卫三. 叶酸受体靶向两亲性嵌段共聚物修饰多烯紫杉醇脂质体的制备及体外性质考察J. 药学学报, 2012,47(9): 1219-1226.
引用本文: 李 翔, 张 婧, 王东凯, 潘卫三. 叶酸受体靶向两亲性嵌段共聚物修饰多烯紫杉醇脂质体的制备及体外性质考察J. 药学学报, 2012,47(9): 1219-1226.
LI Xiang, ZHANG Jing, WANG Dong-kai, PAN Wei-san. Preparation and in vitro properties of folate receptor targeting docetaxel-loaded amphiphilic copolymer-modified liposomesJ. 药学学报, 2012,47(9): 1219-1226.
Citation: LI Xiang, ZHANG Jing, WANG Dong-kai, PAN Wei-san. Preparation and in vitro properties of folate receptor targeting docetaxel-loaded amphiphilic copolymer-modified liposomesJ. 药学学报, 2012,47(9): 1219-1226.

叶酸受体靶向两亲性嵌段共聚物修饰多烯紫杉醇脂质体的制备及体外性质考察

Preparation and in vitro properties of folate receptor targeting docetaxel-loaded amphiphilic copolymer-modified liposomes

  • 摘要:

    以合成的两亲性嵌段共聚物叶酸-聚乙二醇-聚胆固醇氰基丙烯酸脂 (FA-PEG-PCHL) 为靶向长循 环膜修饰材料, 采用有机溶剂注入法制备FA-PEG-PCHL修饰的多烯紫杉醇脂质体 (FA-PDCT-L), 利用星点设 -效应面优化法筛选最优处方, 并通过FT-IR1H NMR对合成产物进行结构确证; 采用超滤法、透射电镜、粒径zeta电位测定仪以及荧光偏振法等考察FA-PDCT-L理化性质。结果显示, 所制备FA-PDCT-L呈球形或类球形, 粒径在111.6126.9 nm, zeta电位在 −6.54 −14.13 mV, 包封率可达97.8%, 各指标实测值与预测值  偏差较小。FA-PEG-PCHL可以降低脂质双分子膜的流动性, 膜流动性与FA-PEG-PCHLPEG分子量呈正相 关。FA-PDCT-L在体外具有明显的缓释效果, 无突释现象, 随着PEG分子量的降低, 24 h累计释放率分别为31.1%27.2% 19.5%, 且稳定性良好。该研究为进一步研究叶酸受体靶向的长循环膜修饰脂质体在肿瘤疾病治疗中的应用打下了基础。

     

    Abstract:

    A novel amphiphilic copolymer, folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized as liposomal modifying material with folate receptor targeting and long circulating property.  FA-PEG-PCHL-modified docetaxel-loaded liposomes (FA-PDCT-L) were prepared by organic solvent injection method, and the system was optimized using central composite design-response surface methodology.  The structure of the FA-PEG-PCHL copolymer was confirmed by FT-IR and 1H NMR.  Ultrafiltration technique, transmission electron microscope, dynamic light scattering and electrophoretic light scattering, and fluorescence polarization method were used to study the physicochemical parameters of FA-PDCT-L.  FA-PDCT-L showed spherical or ellipsoid shape.  The mean particle sizes were in the range of 111.6 − 126.9 nm, zeta potentials were from −6.54 mV to −14.13 mV and the drug encapsulation efficiency achieved 97.8%.  The observed values agreed well with model predicted values.  The membrane fluidity increased with the increment of the molecular weight of PEG and the decrement of the amount of FA-PEG-PCHL.  The in vitro release test showed that the drug could be sustained-released from liposomes without a burst release and with stability for 6 months.  After 24 h only 31.1%, 27.2% and 19.5% of encapsulated docetaxel were released for FA-PDCT10000-L, FA-PDCT4000-L and FA-PDCT2000-L, respectively.  This work is useful for further research on the application of the synthesized copolymer-modified long circulating liposomes for cancer therapy.

     

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