Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, Tromsø, Norway.
J Liposome Res. 2013 Mar;23(1):70-81. doi: 10.3109/08982104.2012.742537. Epub 2012 Dec 5.
Camptothecin (CPT) represents a potent anticancer drug. However, its therapeutic use is impaired by both drug solubility, hydrolysis, and protein interactions in vivo. Use of liposomes as a drug-formulation approach could overcome some of these challenges. The aim of this study was to perform a mechanistic study of the incorporation and retention of the lipophilic parent CPT compound in different liposome formulations using radiolabeled CPT and thus to be able to identify promising CPT delivery systems. In this context, we also wanted to establish an appropriate mouse tumor model, in vivo scintigraphic imaging, and biodistribution methodology for testing the most promising formulation. CPT retention in various liposome formulations after incubation in buffer and serum was determined. The HT-29 mouse tumor model, (111)In-labeled liposomes, as well as (3)H-labeled CPT were used to investigate the biodistribution of liposomes and drug. The ability of different liposome formulations to retain CPT in buffer was influenced by lipid concentration and drug/lipid ratio, rather than lipid composition. The tested formulations were cleared from the blood in the following order: CPT solution > CPT liposomes > (111)In-labeled liposomes, and liposomes mainly accumulated in the liver. Lipid composition did not influence CPT retention to the same extent as earlier observed from incorporation studies. The set-up for the biodistribution study works well and is suited for future in vivo studies on CPT liposomes. The biodistribution study showed that liposomes circulated longer than free drug, but premature release of drug from liposomes occurred. Further studies to develop formulations with higher retention potential and prolonged circulation are desired.
喜树碱（CPT）是一种有效的抗癌药物。然而，其在体内的治疗用途受到药物溶解度、水解和蛋白质相互作用的限制。使用脂质体作为药物制剂方法可以克服其中的一些挑战。本研究旨在通过使用放射性标记的 CPT 对不同脂质体制剂中亲脂性母体 CPT 化合物的掺入和保留进行机制研究，从而能够鉴定有前途的 CPT 递药系统。在这方面，我们还希望建立一个合适的小鼠肿瘤模型，用于体内闪烁成像和生物分布方法学，以测试最有前途的制剂。在缓冲液和血清中孵育后，确定了不同脂质体制剂中 CPT 的保留情况。使用 HT-29 小鼠肿瘤模型、（111）In 标记的脂质体以及（3）H 标记的 CPT 来研究脂质体和药物的生物分布。不同脂质体制剂在缓冲液中保留 CPT 的能力受脂质浓度和药物/脂质比的影响，而不受脂质组成的影响。以以下顺序从血液中清除测试制剂：CPT 溶液>CPT 脂质体>（111）In 标记的脂质体，并且脂质体主要积聚在肝脏中。脂质组成对 CPT 保留的影响不如以前在掺入研究中观察到的那样大。生物分布研究的设置效果很好，适合未来关于 CPT 脂质体的体内研究。生物分布研究表明，脂质体的循环时间长于游离药物，但脂质体过早释放药物。需要进一步研究开发具有更高保留潜力和延长循环时间的制剂。
