Younis Mona K, Elakkad Yara E, Fakhr Eldeen Rasha R, Ali Isra H, Khalil Islam A
Department of Pharmaceutics, College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology, 6th of October City 12566, Egypt.
Department of Biochemistry, College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology, 6th of October City 12566, Egypt.
Pharmaceutics. 2023 Jul 28;15(8):2033. doi: 10.3390/pharmaceutics15082033.
This study aims at preparing propranolol-loaded trehalosomes (a trehalose-coated liposome) to be used as an antiproliferative agent for treating skin cancer. A factorial design was used to select the optimum formula, where trehalose, lecithin, and Tween 80 levels were studied. A total of 24 runs were prepared and characterized according to size, charge, entrapment efficiency, and release after 3 h to select the optimum formula. The optimized formula was investigated using TEM, DSC, and FTIR. Cell studies were carried out against the human melanoma cell line to measure cytotoxicity, apoptosis/necrosis, and cell cycle arrest. In silico studies were conducted to understand the interaction between propranolol and the influential receptors in melanoma. The results showed the selected formula consisted of trehalose (175 mg), lecithin (164 mg), and Tween 80 (200 mg) with a size of 245 nm, a charge of -9 mV, an EE% of 68%, and a Q3 of 62%. Moreover, the selected formula has good cytotoxicity compared to the free drug due to the synergistic effect of the drug and the designed carrier. IC of free propranolol and the encapsulation of propranolol were 17.48 μg/mL and 7.26 μg/mL, respectively. Also, propranolol and the encapsulation of propranolol were found to significantly increase early and late apoptosis, in addition to inducing G1 phase cell cycle arrest. An in silico virtual study demonstrated that the highest influential receptors in melanoma were the vitamin D receptor, CRH-R1, VEGFR 1, and c-Kit, which matches the results of experimental apoptotic and cell cycle analysis. In conclusion, the selected formula has good cytotoxicity compared to the free drug due to the synergistic effect of the drug and the designed carrier, which make it a good candidate as an antiproliferative agent for treating skin cancer.
本研究旨在制备负载普萘洛尔的海藻糖脂质体（一种海藻糖包被的脂质体），用作治疗皮肤癌的抗增殖剂。采用析因设计来选择最佳配方，研究了海藻糖、卵磷脂和吐温80的用量水平。共制备了24个批次，并根据粒径、电荷、包封率和3小时后的释放情况进行表征，以选择最佳配方。使用透射电子显微镜（TEM）、差示扫描量热法（DSC）和傅里叶变换红外光谱法（FTIR）对优化后的配方进行研究。针对人黑色素瘤细胞系进行细胞研究，以测定细胞毒性、凋亡/坏死情况以及细胞周期阻滞。开展计算机模拟研究以了解普萘洛尔与黑色素瘤中有影响的受体之间的相互作用。结果显示，所选配方包含海藻糖（175毫克）、卵磷脂（164毫克）和吐温80（200毫克），粒径为245纳米，电荷为 -9毫伏，包封率为68%，3小时释放量为62%。此外，由于药物与设计载体的协同作用，所选配方与游离药物相比具有良好的细胞毒性。游离普萘洛尔的半数抑制浓度（IC）和普萘洛尔包封物的IC分别为17.48微克/毫升和7.26微克/毫升。此外，发现普萘洛尔及其包封物除了诱导G1期细胞周期阻滞外，还能显著增加早期和晚期凋亡。计算机模拟虚拟研究表明，黑色素瘤中最具影响力的受体是维生素D受体、促肾上腺皮质激素释放激素受体1（CRH-R1）、血管内皮生长因子受体1（VEGFR 1）和原癌基因c-Kit，这与实验性凋亡和细胞周期分析结果相符。总之，由于药物与设计载体的协同作用，所选配方与游离药物相比具有良好的细胞毒性，使其成为治疗皮肤癌的抗增殖剂的良好候选物。
