Zaher Sara, Soliman Mahmoud E, Elsabahy Mahmoud, Hathout Rania M
Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut 71515, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Pharmaceuticals (Basel). 2022 Jun 10;15(6):733. doi: 10.3390/ph15060733.
The current study evaluated the ability of sesamol-loaded albumin nanoparticles to impart protection against oxidative stress induced by anthracyclines in comparison to the free drug. Albumin nanoparticles were prepared via the desolvation technique and then freeze-dried with the cryoprotectant, trehalose. Albumin concentration, pH, and type of desolvating agent were assessed as determining factors for successful albumin nanoparticle fabrication. The optimal nanoparticles were spherical in shape, and they had an average particle diameter of 127.24 ± 2.12 nm with a sesamol payload of 96.89 ± 2.4 μg/mg. The drug cellular protection was tested on rat hepatocytes pretreated with 1 µM doxorubicin, which showed a 1.2-fold higher protective activity than the free sesamol. In a pharmacokinetic study, the loading of a drug onto nanoparticles resulted in a longer half-life and mean residence time, as compared to the free drug. Furthermore, in vivo efficacy and biochemical assessment of lipid peroxidation, cardiac biomarkers, and liver enzymes were significantly ameliorated after administration of the sesamol-loaded albumin nanoparticles. The biochemical assessments were also corroborated with the histopathological examination data. Sesamol-loaded albumin nanoparticles, prepared under controlled conditions, may provide an enhanced protective effect against off-target doxorubicin toxicity.
本研究评估了负载芝麻酚的白蛋白纳米粒与游离药物相比,赋予对蒽环类药物诱导的氧化应激的保护能力。通过去溶剂化技术制备白蛋白纳米粒,然后与冷冻保护剂海藻糖一起冻干。评估白蛋白浓度、pH值和去溶剂化剂类型作为成功制备白蛋白纳米粒的决定因素。最佳纳米粒呈球形,平均粒径为127.24±2.12nm,芝麻酚有效载荷为96.89±2.4μg/mg。在经1μM阿霉素预处理的大鼠肝细胞上测试药物细胞保护作用,结果显示其保护活性比游离芝麻酚高1.2倍。在药代动力学研究中,与游离药物相比,将药物负载到纳米粒上导致半衰期和平均驻留时间更长。此外,在给予负载芝麻酚的白蛋白纳米粒后,体内疗效以及脂质过氧化、心脏生物标志物和肝酶的生化评估均得到显著改善。生化评估也得到了组织病理学检查数据的证实。在受控条件下制备的负载芝麻酚的白蛋白纳米粒可能对阿霉素的脱靶毒性提供增强的保护作用。