Thermodynamic Limits on Drug Loading in Nanoparticle Cores
Thermodynamic Limits on Drug Loading in Nanoparticle Cores
复制标题
DOI：
10.1002/jps.21342
复制
发表时间：
2008-11-01
影响因子：
3.8
通讯作者：
Prud'Homme, Robert K.
中科院分区：
文献类型：
--
作者：
Kumar, Varun;Prud'Homme, Robert K.
近年来，基于嵌段共聚物的可生物降解纳米粒作为有效的药物载体引起了人们的关注。最大限度地增加载药量是理想的目标，但实验发现载药量只有3%到25wt%(对于紫杉醇)。装载量低和装载量变化的原因尚未得到充分解释。在这项研究中，提出了一个模型，定量地解释了观察到的现象。药物载药的热力学模型是以药物的摩尔自由能为基础的，它取决于嵌段共聚物的大小(熵项)、药物与疏水核之间的相互作用参数(热项)以及载药的压力-体积功。压力-体积功直接与核心和电晕区域之间的界面张力有关，以前没有考虑到药物负载。为了验证模型的有效性，将紫杉醇等有机溶质负载到聚乙二醇聚己内酯、聚乙二醇己内酯嵌段共聚物胶束中的计算结果与实验结果进行了比较。建立的模型预测的负荷值与文献报道的实验结果非常一致。(C)2008 Wiley-Liss，Inc.和美国药剂师协会药学杂志97：4904-4914,2008
Recently, biodegradable nanoparticles based on block copolymers have attracted attention as effective drug delivery vehicles. Maximizing the amount of drug loaded into particle is the desired goal, but loadings of only between 3 to about 25 wt% drug (for paclitaxel) are found experimentally. The reasons for the low loading and variability in loading have not been fully explained. In this study, a model is presented that quantitatively explains the observed phenomena. The thermodynamic model of drug loading is based on the molar free energy of the drug, which depends on the block copolymers size (entropic term), the interaction parameter between the drug and the hydrophobic core (enthalpic term), and the pressure-volume work to load the particle. The pressure-volume work, related directly to the interfacial tension between the core and the corona region, has not been previously considered with respect to drug loading. To validate the model, calculations were compared with experimental results for organic solutes, including paclitaxel, loaded into poly(ethylene glycol)-b-poly(epsilon-caprolactone), PEG-b-PCL block copolymer micelles. The model developed was found to predict the loading values in close agreement with experiments reported in the literature. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4904-4914, 2008