水溶性药物的疏水性修饰及其重组型脂质体的研究

HYDROPHOBIC MODIFICATION OF WATER SOLUBLE DRUG AND ITS RECONSTITUTABLE LIPOSOMES

脂质体载水溶性药物出现的共同问题是药物的包封量低、稳定性差。本文以甲硝唑(Ⅰ)为水溶性药物模型,进行疏水性结构修饰,得其肉豆蔻酸酯(Ⅱ)前体药物,分别进行Ⅰ和Ⅱ的脂质体研究,结果表明Ⅱ在脂质体中的包封率较Ⅰ提高10倍以上,渗漏速率降至十分之一,制成含Ⅱ的脂质干膜,经超声分散,可得合乎要求的重组型脂质体,为解决脂质体载药的稳定性问题提供有效途径。体外抗阿米巴原虫试验,镜检观察到载药脂质体进入阿米巴原虫的细胞内,且100%抑制原虫所需剂量Ⅱ脂质体是Ⅰ游离药的二分之一。因此药物疏水化修饰是解决脂质体载水溶性药物稳定性问题的理想途径。

Water soluble drugs carried in liposomes have rather low encapsulation percentage (EP%) and poor stability. In this paper metronidazole (Ⅰ) was chosen as a model of water soluble drugs which was modified by means of esterification. Its myristic ester (Ⅱ) was synthesized. On studying the liposomes of Ⅰ and Ⅱ, the results have shown that EP% and stability of Ⅱ were more than ten times as high as that of Ⅰ. Furthermore, the reconstitutable liposomes of Ⅱ were prepared successfully. The amoebacide activity of Ⅱ liposomes was increased also. Therefore, the hydrophobic modification of water soluble drugs is a good way to improve the drug entrapped in liposomes.