Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Multan, Pakistan.
Institute of Chemical Science, Bahauddin Zakariya University Multan, Multan, Pakistan.
AAPS PharmSciTech. 2023 Jun 22;24(6):141. doi: 10.1208/s12249-023-02588-7.
Inhibition of melanogenesis by quercetin and vitamin E is extensively reported in the literature, independently, with limitations in antioxidant potential owing to less permeation, solubility, decreased bioavailability, and reduced stability. Thus, the aim of the present study was to synthesize a novel complex of metal ions (copper and zinc) with quercetin to enhance antioxidant properties which were confirmed by docking studies. Polycaprolactone-based nanoparticles of the synthesized complex (PCL-NPs, Q-PCL-NPs, Zn-Q-PCL-NPs, Cu-Q-PCL-NPs) were made later loaded with vitamin E which made the study more interesting in enhancing antioxidant profile. Nanoparticles were characterized for zeta size, charge, and polydispersity index, while physiochemical analysis of nanoparticles was strengthened by FTIR. Cu-Q-PCL-NPs-E showed maximum in vitro release of vitamin E, i.e., 80 ± 0.54%. Non-cellular antioxidant effect by 2,2-diphenyl-1-picrylhydrazyl was observed at 93 ± 0.23% in Cu-Q-PCL-NPs-E which was twofold as compared to Zn-Q-PCL-NPs-E. Michigan Cancer Foundation-7 (MCF-7) cancer cell lines were used to investigate the anticancer and cellular antioxidant profile of loaded and unloaded nanoparticles. Results revealed reactive oxygen species activity of 90 ± 0.32% with the addition of 89 ± 0.64% of its anticancer behavior shown by Cu-Q-PCL-NPs-E after 6 and 24h. Similarly, 80 ± 0.53% inhibition of melanocyte cells and 95 ± 0.54% increase of keratinocyte cells were also shown by Cu-Q-PCL-NPs-E that confirmed the tyrosinase enzyme inhibitory effect. Conclusively, the use of zinc and copper complex in unloaded and vitamin E-loaded nanoparticles can provide enhanced antioxidant properties with inhibition of melanin, which can be used for treating diseases of melanogenesis.
槲皮素和维生素 E 抑制黑色素生成在文献中被广泛报道,各自具有局限性,由于渗透能力较低、溶解度较低、生物利用度降低以及稳定性降低,抗氧化潜力有限。因此,本研究的目的是合成一种新型的金属离子(铜和锌)与槲皮素的复合物,以增强抗氧化特性,这一点通过对接研究得到了证实。后来,用维生素 E 负载合成的复合物(PCL-NPs、Q-PCL-NPs、Zn-Q-PCL-NPs、Cu-Q-PCL-NPs)制成了聚己内酯纳米粒子,这使得研究在增强抗氧化特性方面更具吸引力。纳米粒子的特性包括 Zeta 粒径、电荷和多分散指数,而纳米粒子的物理化学分析则通过傅里叶变换红外光谱得到加强。Cu-Q-PCL-NPs-E 表现出最大的维生素 E 体外释放,即 80±0.54%。通过 2,2-二苯基-1-苦基肼观察到非细胞抗氧化作用,在 Cu-Q-PCL-NPs-E 中达到 93±0.23%,是 Zn-Q-PCL-NPs-E 的两倍。密歇根癌症基金会-7(MCF-7)癌细胞系用于研究负载和未负载纳米粒子的抗癌和细胞抗氧化特性。结果表明,在添加 89±0.64%的活性氧物质后,Cu-Q-PCL-NPs-E 表现出 90±0.32%的活性氧物质活性,并且在 6 和 24 小时后表现出 89±0.64%的抗癌作用。同样,Cu-Q-PCL-NPs-E 还表现出 80±0.53%的黑色素细胞抑制和 95±0.54%的角质形成细胞增加,这证实了酪氨酸酶抑制作用。总之,未负载和负载维生素 E 的纳米粒子中锌和铜复合物的使用可以提供增强的抗氧化特性,同时抑制黑色素生成,可用于治疗黑色素生成疾病。