Structural characterisation of nucleoside loaded low density lipoprotein as a main criterion for the applicability as drug delivery system
Structural characterisation of nucleoside loaded low density lipoprotein as a main criterion for the applicability as drug delivery system
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DOI：
10.1016/s0009-3084(03)00002-1
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发表时间：
2003-04-01
影响因子：
3.4
通讯作者：
Prassl, R
中科院分区：
文献类型：
--
作者：
Hammel, M;Laggner, P;Prassl, R
人类低密度脂蛋白(LDL)颗粒作为亲脂性、细胞毒性药物的递送系统的潜在作用关键取决于它们的结构完整性。在本研究中，低密度脂蛋白颗粒通过不同的技术负载了抗肿瘤前药，即单油酰基(MOT)和二油酰基(DOT)胸苷酯。使用重组方法，MOT显示出最高的参入效率，80%以上的初始药物与低密度脂蛋白有关。相比之下，对于亲脂性较强的DOT，重组、干膜和二甲基亚砜的掺入效率都非常低。用差示扫描量热法(DSC)和小角X射线散射法(SAXS)监测载药后的结构变化。结果表明，MOT和DOT的影响主要限于低密度脂蛋白的表面单层，被认为是蛋白质部分的不稳定和颗粒直径的小幅增加。低密度脂蛋白-药物复合体的核心类脂区域基本上不受影响，核心类脂排列和核心类脂融化行为未受干扰。(C)2003爱思唯尔爱尔兰科学有限公司。保留所有权利。
The potential role of human low density lipoprotein (LDL) particles as delivery system for lipophilic, cytotoxic drugs critically depends on their structural integrity. In the present study, LDL particles were loaded with antineoplastic prodrugs, i.e. monooleoyl (MOT)- and dioleoyl (DOT)- thymidine esters by different techniques. Using the reconstitution method MOT shows the highest incorporation efficiency with over 80% of the initial drug associated with LDL. In contrast, for the more lipophilic DOT the incorporation efficiency for reconstitution, dry film as well as dimethylsulfoxide method was extremely low. Structural changes upon drug loading were monitored by differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). The results show that the influence of MOT and DOT is predominantly confined to the surface monolayer of LDL seen as a destabilisation of the protein moiety and a small increase in particle diameter. The core lipid region of the LDL-drug complexes remains essentially unaffected, as verified by undisturbed core lipid arrangement and core lipid melting behaviour. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.