Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Vitiligo Research Chair, Department of Dermatology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia.
Molecules. 2023 Feb 28;28(5):2237. doi: 10.3390/molecules28052237.
Oral anticancer therapy mostly faces the challenges of low aqueous solubility, poor and irregular absorption from the gastrointestinal tract, food-influenced absorption, high first-pass metabolism, non-targeted delivery, and severe systemic and local adverse effects. Interest has been growing in bioactive self-nanoemulsifying drug delivery systems (bio-SNEDDSs) using lipid-based excipients within nanomedicine. This study aimed to develop novel bio-SNEDDS to deliver antiviral remdesivir and baricitinib for the treatment of breast and lung cancers. Pure natural oils used in bio-SNEDDS were analyzed using GC-MS to examine bioactive constituents. The initial evaluation of bio-SNEDDSs were performed based on self-emulsification assessment, particle size analysis, zeta potential, viscosity measurement, and transmission electron microscopy (TEM). The single and combined anticancer effects of remdesivir and baricitinib in different bio-SNEDDS formulations were investigated in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines. The results from the GC-MS analysis of bioactive oils BSO and FSO showed pharmacologically active constituents, such as thymoquinone, isoborneol, paeonol and p-cymenene, and squalene, respectively. The representative F5 bio-SNEDDSs showed relatively uniform, nanosized (247 nm) droplet along with acceptable zeta potential values (+29 mV). The viscosity of the F5 bio-SNEDDS was recorded within 0.69 Cp. The TEM suggested uniform spherical droplets upon aqueous dispersions. Drug-free, remdesivir and baricitinib-loaded bio-SNEDDSs (combined) showed superior anticancer effects with IC50 value that ranged from 1.9-4.2 µg/mL (for breast cancer), 2.4-5.8 µg/mL (for lung cancer), and 3.05-5.44 µg/mL (human fibroblasts cell line). In conclusion, the representative F5 bio-SNEDDS could be a promising candidate for improving the anticancer effect of remdesivir and baricitinib along with their existing antiviral performance in combined dosage form.
口服抗癌疗法主要面临水溶解度低、胃肠道吸收差且不规则、受食物影响的吸收、高首过代谢、非靶向递送以及严重的全身和局部不良反应等挑战。利用纳米医学中的基于脂质的赋形剂，生物活性自微乳给药系统（bio-SNEDDS）受到越来越多的关注。本研究旨在开发新型 bio-SNEDDS 以递送抗病毒药物瑞德西韦和巴瑞替尼，用于治疗乳腺癌和肺癌。使用 GC-MS 分析 bio-SNEDDS 中使用的纯天然油，以检查生物活性成分。根据自乳化评估、粒径分析、zeta 电位、粘度测量和透射电子显微镜（TEM）对 bio-SNEDDS 进行初步评估。在 MDA-MB-231（乳腺癌）和 A549（肺癌）细胞系中研究了瑞德西韦和巴瑞替尼在不同 bio-SNEDDS 制剂中的单一和联合抗癌作用。GC-MS 分析生物活性油 BSO 和 FSO 的结果分别显示出具有药理学活性的成分，如百里醌、异龙脑、丹皮酚和对伞花烃，以及角鲨烯。代表性的 F5 bio-SNEDDS 显示出相对均匀的纳米尺寸（247nm）液滴以及可接受的 zeta 电位值（+29mV）。F5 bio-SNEDDS 的粘度记录在 0.69Cp 内。TEM 表明水相分散后形成均匀的球形液滴。无药物、瑞德西韦和巴瑞替尼负载的 bio-SNEDDS（组合）表现出优异的抗癌作用，IC50 值范围为 1.9-4.2µg/mL（用于乳腺癌）、2.4-5.8µg/mL（用于肺癌）和 3.05-5.44µg/mL（人成纤维细胞系）。总之，代表性的 F5 bio-SNEDDS 可能是一种有前途的候选药物，可提高瑞德西韦和巴瑞替尼的抗癌效果，并在联合剂型中发挥其现有的抗病毒性能。
