Ahmad Ajaz, Jan Basit Latief, Raish Mohammad, Rachamalla Hari Krishna Reddy, Banerjee Rajkumar, Mukhopadhyay Debabrata, Alkharfy Khalid M
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Saudi Pharm J. 2019 Jul;27(5):637-642. doi: 10.1016/j.jsps.2019.03.005. Epub 2019 Mar 11.
The genotoxic potential of glucocorticoid receptor (GR)-targeted liposomal formulations of the anticancer drug molecule ESC8 was studied . A methodical literature review discovered no previous studies on the genotoxicity of ESC8. Genotoxicity was assessed in both male and female mice by various assay systems, such as comet assay, chromosomal aberrations and micronuclei assay, which detect different abnormalities. Eleven groups of male mice and eleven groups of female mice, containing six animals per group, were used in the present study: group I served as vehicle control; group II received the positive control (cyclophosphamide 40 mg/kg; CYP); and animals in group III to XI received free drug (ESC8), DX liposome and drug-associated DX liposomal formulation (DXE), respectively, dissolved in 5% solution of glucose at a drug-dose of 1.83, 3.67 and 7.34 mg/kg, respectively. Same drug treatments were followed for the female mice groups. The obtained data revealed the safety of DXE, which did not show substantial genotoxic effects at different dose levels. In contrast, the positive control, CYP, exhibited highly substantial irregular cytogenetic variations in comparison with the control group in different assays.
研究了抗癌药物分子ESC8的糖皮质激素受体（GR）靶向脂质体制剂的遗传毒性潜力。系统的文献综述发现，之前没有关于ESC8遗传毒性的研究。通过各种检测系统，如彗星试验、染色体畸变和微核试验，在雄性和雌性小鼠中评估遗传毒性，这些检测系统可检测不同的异常情况。本研究使用了11组雄性小鼠和11组雌性小鼠，每组6只动物：第一组作为溶剂对照组；第二组接受阳性对照（环磷酰胺40mg/kg；CYP）；第三组至第十一组的动物分别接受游离药物（ESC8）、DX脂质体和药物相关DX脂质体制剂（DXE），分别溶解于5%葡萄糖溶液中，药物剂量分别为1.83、3.67和7.34mg/kg。雌性小鼠组采用相同的药物处理。获得的数据显示DXE是安全的，在不同剂量水平下未显示出明显的遗传毒性作用。相比之下，阳性对照CYP在不同检测中与对照组相比表现出高度明显的不规则细胞遗传学变异。
