Faculty of Pharmacy (FFUC), Department of Pharmaceutical Technology, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Int J Mol Sci. 2020 Feb 20;21(4):1449. doi: 10.3390/ijms21041449.
In this work, we developed a solid lipid nanoparticle (SLN) formulation with (+)-limonene 1,2-epoxide and glycerol monostearate (-SLNs), stabilized with Poloxamer 188 in aqueous dispersion to modify the release profile of the loaded monoterpene derivative. We also evaluated the role of SLNs in lipid peroxidation and cytotoxicity in a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (the HaCaT cell line). For the cell viability assay, the colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. -SLNs with a loading capacity and encapsulation efficiency of 0.39% and 63%, respectively, were produced by high pressure homogenization. A mean particle size of 194 ± 3.4 nm and polydispersity index of 0.244 were recorded for the loaded -SLNs, as compared to 203 ± 1.5 nm (PI 0.213) for the non-loaded (blank) SLNs. The loading of the monoterpene derivative into glycerol monostearate SLNs fitted into the zero-order kinetics, and ameliorated both lipid peroxidation and cytotoxicity in a keratinocyte cell line. A promising formulation for antioxidant and anti-tumoral activities is here proposed.
在这项工作中,我们开发了一种固体脂质纳米粒(SLN)制剂,其中含有(+)-柠檬烯 1,2-环氧化物和甘油单硬脂酸酯(-SLNs),并在水性分散体中用泊洛沙姆 188 稳定,以改变负载单萜衍生物的释放特性。我们还评估了 SLNs 在自发性转化的人成纤维细胞永生化细胞系(HaCaT 细胞系)中脂质过氧化和细胞毒性中的作用。对于细胞活力测定,使用比色法 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴盐(MTT)测定法。通过高压匀浆生产了载药量和包封效率分别为 0.39%和 63%的 -SLNs。负载 -SLNs 的平均粒径为 194 ± 3.4nm,多分散指数为 0.244,而非负载(空白)SLNs 的粒径为 203 ± 1.5nm(PI 0.213)。单萜衍生物在甘油单硬脂酸酯 SLNs 中的负载符合零级动力学,改善了角质形成细胞系中的脂质过氧化和细胞毒性。本文提出了一种具有抗氧化和抗肿瘤活性的有前途的制剂。