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目的：研制出包封率高，逃避体内网状内皮系统捕获的“隐形”（ｓｔｅａｌｔｈ）脂质体并考察其在生物体内的组织分布。方法：以化学梯度法包封脂质体，用两亲性聚乙二醇－二硬脂酰磷脂酰乙醇胺（ＰＥＧ－ＤＳＰＥ）对脂质体膜进行修饰以制备隐形脂质体；用ＨＰＬＣ－ＵＶ法测定给药后小鼠体内组织中的药物浓度。结果：制备的阿霉素隐形脂质体包封率达９７％以上；与普通脂质体及游离的阿霉素相对照，隐形脂质体在血液中循环时间显著地延长，血药浓度－时间曲线下面积（ＡＵＣ）显著增加，三种制剂在小鼠的心、肝、脾、肺、肾组织中的分布特性有不同程度的改变。结论：这种化学梯度法可以较大地提高包封率。隐形脂质体血液ＡＵＣ增加，可延长药物在体内循环时间；心脏组织分布浓度低，可降低心脏毒性。
OBJECTIVE: To develop “stealth” liposomes with high entrapment efficiency and escape from the reticuloendothelial system in vivo, and to investigate their tissue distribution in vivo. METHODS: Liposomes were encapsulated by chemical gradient method. Liposome membranes were modified with amphipathic polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) to prepare in-liposomes. HPLC- UV method to determine the concentration of drug in the tissues of mice after administration. Results: The encapsulation efficiency of doxorubicin stealth liposomes was over 97%. Compared with the ordinary liposomes and free doxorubicin, the stealth liposomes had a significantly longer circulating time in the blood and the plasma concentration- The area under the curve of time (AUC) increased significantly. The distribution characteristics of three preparations in mice heart, liver, spleen, lung and kidney varied to some extent. Conclusion: This chemical gradient method can greatly improve the entrapment efficiency. Invisible liposome blood AUC increased, can extend the drug in vivo circulation time; low concentration of cardiac tissue distribution, can reduce cardiac toxicity.