In the present study, we investigated the role of lipid composition of camptothecin (CPT)-loaded liposomes (CPT-Lips) to adjust their residence time, drug distribution, and therefore the toxicities and antitumor activity. The CPT was loaded into liposomes using a click drug loading method, which utilized liposomes preloaded with GSH and then exposed to CPT-maleimide. The method produced CPT-Lips with a high encapsulation efficiency (>95%) and sustained drug release. It is shown that the residence times of CPT-Lips in the body were highly dependent on lipid compositions with an order of non-PEGylated liposomes of unsaturated lipids < non-PEGylated liposomes of saturated lipids < PEGylated liposomes of saturated lipids. Interestingly, the fast clearance of CPT-Lips resulted in significantly decreased toxicities but did not cause a significant decrease in their in vivo antitumor activity. These results suggested that the lipid composition could effectively adjust the residence time of CPT-Lips in the body and further optimize their therapeutic index, which would guide the development of a liposomal formulation of CPT.

中文翻译：

---

脂质成分对主动点击加载喜树碱脂质体递送的影响

在本研究中，我们研究了喜树碱（CPT）负载脂质体（CPT-Lips）的脂质成分在调整其停留时间、药物分布以及毒性和抗肿瘤活性方面的作用。使用点击药物装载方法将 CPT 装载到脂质体中，该方法利用预装载 GSH 的脂质体，然后暴露于 CPT-马来酰亚胺。该方法生产的CPT-Lips具有高包封率（>95%）和持续的药物释放。结果表明，CPT-Lips在体内的停留时间高度依赖于脂质成分，其顺序为：非聚乙二醇化不饱和脂质脂质体<非聚乙二醇化饱和脂质脂质体<聚乙二醇化饱和脂质脂质体。有趣的是，CPT-Lips 的快速清除导致毒性显着降低，但并未导致其体内抗肿瘤活性显着降低。这些结果表明，脂质组合物可以有效调节喜树碱-Lips在体内的停留时间，并进一步优化其治疗指数，这将指导喜树碱脂质体制剂的开发。