Lipid core nanoparticles resembling low-density lipoprotein and regression of atherosclerotic lesions: effects of particle size.
Lipid core nanoparticles resembling low-density lipoprotein and regression of atherosclerotic lesions: effects of particle size.
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DOI：
10.1590/1414-431x20177090
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发表时间：
2018-01-23
期刊：
影响因子：
--
通讯作者：
Maranhão RC
中科院分区：
文献类型：
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作者：
Freitas SCMP;Tavares ER;Silva BMO;Meneghini BC;Kalil-Filho R;Maranhão RC
颗粒通常是多分散的，并且尺寸是基于脂质的药物递送系统的重要特征，以优化细胞-颗粒相互作用，如药理作用和毒性。脂质纳米粒（LDE）的组成类似于低密度脂蛋白载紫杉醇，显着减少动脉粥样硬化病变的兔胆固醇喂养。本研究的目的是测试两种LDE组分（一种具有小颗粒（20-60 nm），另一种具有大颗粒（60-100 nm）是否对动脉粥样硬化病变具有不同的作用。通过密度梯度超离心分离通过微流化制备的两种LDE-紫杉醇级分，并将其注射（4 mg/体重，每周静脉注射一次）到先前喂食胆固醇4周的两组家兔中。将一组注射盐水溶液的胆固醇喂养动物用作对照，以评估治疗的病变减少。给药期后，对动物实施安乐死以进行分析。治疗后，LDE-紫杉醇的小和大纳米粒制剂具有同样强的抗动脉粥样硬化作用。两种药物均使主动脉中的病变扩展减少约50%，内膜宽度减少75%，内膜中的巨噬细胞减少50%。两种制剂也显示出相似的毒性特征。总之，在20-100 nm范围内，尺寸显然不是LDE纳米颗粒系统的重要特征，可能也不是其他基于固体脂质的系统的重要特征。
Particles are usually polydispersed and size is an important feature for lipid-based drug delivery systems in order to optimize cell-particle interactions as to pharmacologic action and toxicity. Lipid nanoparticles (LDE) with composition similar to that of low-density lipoprotein carrying paclitaxel were shown to markedly reduce atherosclerosis lesions induced in rabbits by cholesterol feeding. The aim of this study was to test whether two LDE fractions, one with small (20–60 nm) and the other with large (60–100 nm) particles, had different actions on the atherosclerotic lesions. The two LDE-paclitaxel fractions, prepared by microfluidization, were separated by density gradient ultracentrifugation and injected (4 mg/body weight, intravenously once a week) into two groups of rabbits previously fed cholesterol for 4 weeks. A group of cholesterol-fed animals injected with saline solution was used as control to assess lesion reduction with treatment. After the treatment period, the animals were euthanized for analysis. After treatment, both the small and large nanoparticle preparations of LDE-paclitaxel had equally strong anti-atherosclerosis action. Both reduced lesion extension in the aorta by roughly 50%, decreased the intima width by 75% and the macrophage presence in the intima by 50%. The two preparations also showed similar toxicity profile. In conclusion, within the 20–100 nm range, size is apparently not an important feature regarding the LDE nanoparticle system and perhaps other solid lipid-based systems.