Synthesis, preformulation and liposomal formulation of cholesteryl carborane esters with various fatty chains
Synthesis, preformulation and liposomal formulation of cholesteryl carborane esters with various fatty chains
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DOI：
10.1016/s0378-5173(03)00088-7
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发表时间：
2003-04-14
影响因子：
5.8
通讯作者：
Lu, DR
中科院分区：
文献类型：
--
作者：
Alanazi, F;Li, HG;Lu, DR
低密度脂蛋白受体在肿瘤细胞上的表达升高，为肿瘤细胞靶向给药提供了一种有吸引力的途径。合适的抗肿瘤化合物。然而。需要合成和开发一种模拟天然胆固醇I酯（作为LDL的主要成分）的化学结构，通过过表达的LDL受体靶向递送到肿瘤细胞。本研究设计了以胆固醇、脂肪链和碳硼烷为抗肿瘤单元的新型抗肿瘤化合物，并采用三步反应方案合成了3种新化合物。与天然胆固醇酯类似，这些化合物是极度疏水的，在任何进一步的生物学研究之前，需要为这些新化合物配制合适的脂质体。因此，各种脂质体制剂以及这些新化合物的制剂前表征进行了检查。发现化合物在脂质体中的掺入效率根据所附脂肪链的类型和用作脂质体制剂辅料的胆固醇：磷脂的比例而显着变化。(C) 2003 Elsevier Science B.V.版权所有
The elevated expression of LDL receptor on tumor cells provides one attractive approach for targeted drug delivery to tumor cells. Suitable antitumor compounds. however. need to be synthesized and developed which mimic the native cholesteryl I esters (as major constituent of LDL) in chemical structure for targeted delivery to tumor cells through the over-expressed LDL receptors. In the present study, new antitumor compounds were designed containing cholesterol, fatty chain and carborane which is used as the antitumor unit, Three new compounds were synthesized with a three-step reaction scheme. Similar to the native cholesteryl esters, these compounds are extremely hydrophobic and, before any further biological studies, suitable liposomal formulations for these new compounds are required. Various liposomal formulations as well as the preformulation characterization of these ne compounds were thus examined. The incorporation efficiency of the compounds in liposomes was found to vary significantly depending on the type of fatty chain attached and the ratio of cholesterol:phospholipid used as the excipients of liposomal formulation. (C) 2003 Elsevier Science B.V. All rights reserved.