Rodenak-Kladniew Boris, Islan German A, de Bravo Margarita G, Durán Nelson, Castro Guillermo R
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, CCT-La Plata, Facultad de Ciencias Médicas, La Plata, Argentina.
Laboratorio de Nanobiomateriales, CINDEFI, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET (CCT La Plata), Calle 47 y 115., C.P. 1900 La Plata, Argentina.
Colloids Surf B Biointerfaces. 2017 Jun 1;154:123-132. doi: 10.1016/j.colsurfb.2017.03.021. Epub 2017 Mar 9.
Linalool (LN) is a monoterpene found in essential oils of plants and herbs that produces multiple effects on the mevalonate pathway and interesting antiproliferative activity in cancer cells. However, due to its poor aqueous solubility, an efficient vehicle is needed to improve its administration and bioavailability in physiological media. LN encapsulation in solid lipid nanoparticles (SLN) with different compositions was explored and in vitro tested in two cancer cell lines. SLN of myristyl myristate (MM), cetyl esters (SS) and cetyl palmitate (CP) were prepared by sonication in the presence of PluronicF68 as surfactant. Nanoparticle size, morphology and distribution were determined by dynamic light scattering in combination with optical and transmission electron microscopy (TEM). SLN showed spherical shape and mean diameters in the range of 90-130nm with narrow size dispersion (PDI values lower than 0.2) and Z potentials around -4.0mV. The encapsulation percentages of LN in SLN were higher than 80% for all tested formulations and exhibited in vitro LN controlled release profiles for at least 72h. The nanoparticles were physicochemically characterized by FTIR, XRD, DSC and TGA, and the incorporation of LN into SLN was higher than 80% in tested matrices. The developed formulations, and in particular SLN (MM)-LN, showed in vitro antiproliferative effects on hepatocarcinoma (HepG2) and lung adenocarcinoma (A549) cell lines in a dose-dependent response, and higher inhibitory effects were found in comparison with free LN. The cellular uptake of SLN was demonstrated by fluorescence microscopy, enhancing the ability of nanoparticles to intracellularly deliver the cargo molecules.
芳樟醇（LN）是一种存在于植物和草药精油中的单萜，它对甲羟戊酸途径具有多种作用，并在癌细胞中展现出有趣的抗增殖活性。然而，由于其水溶性较差，需要一种有效的载体来改善其在生理介质中的给药方式和生物利用度。研究了将LN包封在不同组成的固体脂质纳米粒（SLN）中，并在两种癌细胞系中进行了体外测试。在表面活性剂普朗尼克F68存在的情况下，通过超声处理制备了肉豆蔻酸肉豆蔻酯（MM）、鲸蜡酯（SS）和十六烷基棕榈酸酯（CP）的纳米粒。通过动态光散射结合光学和透射电子显微镜（TEM）来确定纳米粒的尺寸、形态和分布。SLN呈球形，平均直径在90 - 130nm范围内，粒径分散窄（PDI值低于0.2），Z电位约为 - 4.0mV。对于所有测试制剂，LN在SLN中的包封率均高于80%，并且在体外呈现出至少72小时的LN控释曲线。通过傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、差示扫描量热法（DSC）和热重分析（TGA）对纳米粒进行了物理化学表征，在测试基质中LN掺入SLN的比例高于80%。所开发的制剂，特别是SLN（MM）-LN，在肝癌（HepG2）和肺腺癌（A549）细胞系中呈现出剂量依赖性的体外抗增殖作用，并且与游离LN相比具有更高的抑制作用。通过荧光显微镜证实了SLN的细胞摄取，增强了纳米粒向细胞内递送货物分子的能力。
