掺入不同形式聚乙二醇的大黄素脂质体的制备与评价

Preparation and evaluation of emodin liposomes mixed with different forms of PEG

目的:制备掺入甲氧基聚乙二醇2000(mPEG2000)、二硬脂酰乙醇胺-聚乙二醇2000(DSPE-PEG2000)、胆固醇-聚乙二醇2000(Chol-PEG2000)3种形式聚乙二醇(Polyethylene glycol,PEG)的大黄素脂质体,并对其制剂学性质与体外释放性能进行评价。方法:采用薄膜分散-超声法制备掺入不同形式PEG的大黄素脂质体,分别为甲氧基聚乙二醇化大黄素脂质体(mPEG-Emo-Lip)、二硬脂酰乙醇胺-聚乙二醇化大黄素脂质体(DSPE-Emo-Lip)、胆固醇-聚乙二醇化大黄素脂质体(CholEmo-Lip);各脂质体采用激光散射法测定粒径,透射电镜扫描法观察形态,微柱离心法考察包封率(entrapped efficiency,EE%)、载药量(eoading capacity,LC)与泄漏率(leakage,LK%)等制剂学性质;采用动态透析法考察各脂质体在pH7.4、pH5.8以及含5%FBS的PBS释放介质中的释放性能。结果:3种脂质体的粒径在120~140 nm之间,分布较均匀,其中mPEGEmo-Lip粒径稍大;各脂质体包封率大于88%,载药量为32.15~32.53 mg·g-1,泄漏率低;在pH7.4、pH5.8以及含5%FBS的PBS释放介质中的释放度均为DSPE-Emo-Lip>mPEG-Emo-Lip>Chol-Emo-Lip。结论:采用薄膜分散-超声法制备含有不同形式PEG的3种大黄素脂质体,均具有较好的制剂学性质,其中Chol-Emo-Lip具有较强的缓释性能。

OBJECTIVE To prepare 3 kinds of emodin liposomes mixed with mPEG2000, DSPE-PEG2000 and Chol- PEG2000, and evaluate their preparation properties and release properties in vitro. METHODS mPEG-Emo-Lip, DSPE-Emo- Lip and Chol-Emo-Lip were prepared by film dispersion-ultrasonic method. The particle sizes were measured with laser scattering method. The morphologies were observed by transmission election microscopy （TEM）. Their entrapped efficiency （EE%）, drug loading capacity （LC） and leakage （LK%） were investigated with mini-column centrifugation method. The re- lease properties of liposomes were inspected in PBS as pH 7.4, pH 5. 8 and 5 %FBS by dynamic dialysis method. RESULTS The particle sizes of 3 kinds of emodin liposomes were in the range of 120-140 um, mPEG-Emo-Lip was larger, and the distri- butions were more homogeneous. The entrapped efficiencies of 3 kinds of emodin liposomes were all above 88%. The drug loading capacity was in the range of 32. 15-32. 53 mg.g-1. The leakage was low. The release rate in PBS as pH 7. 4, pH 5.8 and 5% FBS were DSPE-Emo-Lip〉mPEG-Emo-Lip〉Chol-Emo-Lip with the same tendency. CONCLUSION The film dis- persion-ultrasonic can be used to prepare 3 kinds of emodin liposomes with good preparation properties, and Chol-Emo-Lip has best sustained-release characters.