Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj-11942, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj-11942, Saudi Arabia.
Chem Phys Lipids. 2020 Nov;233:105003. doi: 10.1016/j.chemphyslip.2020.105003. Epub 2020 Oct 20.
Brigatinib (BG) is a tyrosine kinase receptor inhibitor act as an antineoplastic agent by blocking the action of an abnormal protein that causes cancer cells to multiply. In the current study, nine formulae of BG loaded solid lipid nanoparticles (SLNs) were developed using 3 factorial design. SLNs were prepared by the solvent emulsification technique using stearic acid as lipid and soya- lecithin as a surfactant, both of these act as independent variables, whereas Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and drug loading (DL) were selected as responses. The particle size was found to be in the nano range (176-787 nm), fairly monodisperse (PDI indices 0.19-0.5), interparticle electrical stability was supported by zeta-potential (+1.78 mV to -15.4 mV), whereas EE and DL were in the range of (61.31-87.87 %) (3.35-31.01 %), respectively. Differential scanning calorimetry (DSC) thermograms indicated the amorphous state of BG in the SLN. Fourier transform infrared spectroscopy (FTIR) spectrums confirm non-interaction between drug and polymer while nuclear magnetic resonance (NMR) spectroscopy study revealed BG incorporation in the SLN. A scanning electron microscope (SEM) image exhibit a spherical shape of SLN. The in-vitro release profile demonstrates a sustained release pattern for the selected BS5 SLNs. MTT assay was performed on the optimized SLNs (BS5) and the results are indicative that BG loaded SLN (BS5) showed better cytotoxicity against A349 lung cell lines while compared to BG suspension and blank SLN. Thus, BG loaded SLNs can find Its better place in the non-small cell lung cancer treatment.
布加替尼（BG）是一种酪氨酸激酶受体抑制剂，通过阻断导致癌细胞增殖的异常蛋白质的作用，发挥抗肿瘤作用。在本研究中，使用 3 因素设计开发了 9 种 BG 负载固体脂质纳米粒（SLN）的配方。通过溶剂乳化技术制备 SLN，硬脂酸作为脂质，大豆卵磷脂作为表面活性剂，这两者都是独立变量，而粒径、多分散指数（PDI）、Zeta 电位、包封效率（EE）和载药量（DL）被选为响应。发现粒径在纳米范围内（176-787nm），相当单分散（PDI 指数为 0.19-0.5），Zeta 电位支持颗粒间的电稳定性（+1.78mV 至-15.4mV），而 EE 和 DL 分别在（61.31%-87.87%）（3.35%-31.01%）范围内。差示扫描量热法（DSC）热谱图表明 BG 在 SLN 中处于无定形状态。傅立叶变换红外光谱（FTIR）光谱证实药物和聚合物之间没有相互作用，而核磁共振（NMR）光谱研究表明 BG 被包封在 SLN 中。扫描电子显微镜（SEM）图像显示 SLN 的球形形状。体外释放曲线表明，所选 BS5 SLN 具有持续释放模式。在优化的 SLN（BS5）上进行了 MTT 测定，结果表明，与 BG 混悬液和空白 SLN 相比，BG 负载的 SLN（BS5）对 A349 肺癌细胞系表现出更好的细胞毒性。因此，BG 负载的 SLN 可能在非小细胞肺癌治疗中找到更好的应用。
