Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Animal Science, Faculty of Agricultural Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
Chem Phys Lipids. 2021 Sep;239:105123. doi: 10.1016/j.chemphyslip.2021.105123. Epub 2021 Aug 14.
Lawsone (LWS) is a naphthoquinone-type dye with potential antitumor activity. LWS is used in cosmetics for coloring hair, skin, and nails. In this study, solid lipid nanoparticles (SLNs) containing LWS were prepared using a hot homogenization technique. Physicochemical properties of LWS-SLNs including encapsulation efficiency (EE), drug loading (DL), size, zeta potential, homogeneity, in vitro release, and kinetics of release were determined. The potential cytotoxic properties of LWS-SLNs were investigated. Comet assay was done to assess the genotoxicity of LWS-SLNs. The scanning electron microscopy (SEM) images revealed that LWS-SLNs were spherical and homogeneously dispersed. The average diameter of free SLNs and LWS-SLNs were 97 ± 1.4 and 127 ± 3.1 nm, respectively with high EE% (95.88 ± 3.29) and a DL of 22.72 ± 1.39 mg/mL of LWS-SLNs. The plain LWS could induce growth inhibition of A549 cells with IC of 17.99 ± 1.11, 13.37 ± 1.22, and 9.21 ± 1.15 μg/mL after 24, 48, and 72 h, respectively, while LWS-SLNs had more cytotoxic effects after 48 h (9.81 ± 1.3 μg/mL). Comet assay represented clear fragmentation in the chromatin of the treated cells. Besides, LWS-SLNs (13.37 ± 1.22 μg/mL) induced ∼52 % apoptosis and even necrosis after 48 h. The qPCR results showed an enhanced downregulation of Bcl-2 and upregulation of Casp 9 due to the treatment of A549 cells with LSW-SLNs. In conclusion, a stable formulation of LWS-SLN was prepared with good physicochemical features and long-term biological effects that candidate it for in vivo trials.
龙血素（LWS）是一种具有潜在抗肿瘤活性的萘醌型染料。LWS 用于化妆品中，用于染发、皮肤和指甲。在这项研究中，使用热熔匀化技术制备了含有 LWS 的固体脂质纳米粒（SLNs）。测定了 LWS-SLNs 的理化性质，包括包封效率（EE）、药物载量（DL）、粒径、Zeta 电位、均匀性、体外释放和释放动力学。研究了 LWS-SLNs 的潜在细胞毒性。彗星试验用于评估 LWS-SLNs 的遗传毒性。扫描电子显微镜（SEM）图像显示，LWS-SLNs 呈球形且均匀分散。游离 SLNs 和 LWS-SLNs 的平均直径分别为 97±1.4nm 和 127±3.1nm，EE%高（95.88±3.29），LWS-SLNs 的 DL 为 22.72±1.39mg/mL。普通 LWS 可诱导 A549 细胞生长抑制，其 IC 在 24、48 和 72 h 分别为 17.99±1.11、13.37±1.22 和 9.21±1.15μg/mL，而 LWS-SLNs 在 48 h 后具有更强的细胞毒性作用（9.81±1.3μg/mL）。彗星试验显示处理细胞的染色质明显碎片化。此外，LWS-SLNs（13.37±1.22μg/mL）在 48 h 后诱导约 52%的细胞凋亡甚至坏死。qPCR 结果显示，由于 LSW-SLNs 处理 A549 细胞，Bcl-2 的下调和 Casp 9 的上调增强。总之，制备了具有良好理化性质和长期生物学效应的 LWS-SLN 稳定制剂，为体内试验提供了候选药物。
