筛选设计优化脂质体,开发并验证高效液相色谱法同时测定依罗替尼和尼克洛酰胺的方法。
Development and validation of HPLC method for simultaneous estimation of erlotinib and niclosamide from liposomes optimized by screening design.
发表日期:2023 Jan 02
作者:
Amruta Prabhakar Padakanti, Sachin Dattaram Pawar, Pramod Kumar, Naveen Chella
来源:
JOURNAL OF LIPOSOME RESEARCH
摘要:
药物耐药性对一线治疗已批准的癌症药物的出现导致临床失败。药物重定位研究导致许多旧药物被用于癌症治疗。将重定位药物(硝酰胺)与一线治疗药物如厄洛替尼氢氯酸盐相结合,通过抑制厄洛替尼氢氯酸盐的获得性耐药性,显示出改善的疗效。但是需要为成功输送药物组合开发敏感、准确和优秀的分析方法和药物输送系统。在当前研究中,开发并验证了一种HPLC方法,用于同时估计硝酰胺和厄洛替尼氢氯酸盐。在333nm处,硝酰胺和厄洛替尼氢氯酸盐的保留时间分别为6.48和7.65分钟。开发的方法快速敏感,可以合理准确地分离两种药物,具有良好的准确性、精密度、鲁棒性和坚固性。使用Plackett-Burman(PBD)筛选设计,以粒径、粒径分布、ζ电位和包裹效率作为反应,以确定影响脂质体配方发展的关键参数。脂质浓度、药物浓度、水合温度和介质体积是影响脂质体颗粒大小、多分散性指数(PDI)、ZP和脂质体的%EE的关键参数。优化的NCM-ERL脂质体显示出粒径(126.05±2.1),PDI(0.498±0.1),ZP(-16.2±0.3)和NCM和ERL的%EE(50.04±2.8和05.42±1.3)。体外释放研究表明,药物负载脂质体的控制释放(24小时内为87.06±9.93%和42.33±0.89%)。
The emerging drug resistance to the approved first-line drug therapy leads to clinical failure in cancer. Drug repurposing studies lead to the identification of many old drugs to be used for cancer treatment. Combining the repurposed drugs (niclosamide) with first-line therapy agents like erlotinib HCl showed improved efficacy by inhibiting erlotinib HCl acquired resistance. But there is a need to develop a sensitive, accurate, and excellent analytical method and drug delivery system for successfully delivering drug combinations. In the current study, an HPLC method was developed and validated for the simultaneous estimation of niclosamide and erlotinib HCl. The retention time of niclosamide and erlotinib hydrochloride was 6.48 and 7.65 min at 333 nm. The developed method was rapid and sensitive to separating the two drugs with reasonable accuracy, precision, robustness, and ruggedness. A Plackett-Burman (PBD) screening design was used to identify the critical parameters affecting liposomal formulation development using particle size, size distribution, zeta potential, and entrapment efficiency as the response. Lipid concentration, drug concentration, hydration temperature, and media volume were critical parameters affecting the particle size, polydispersity index (PDI), ZP, and %EE of the liposomes. The optimized NCM-ERL liposomes showed the particle size (126.05 ± 2.1), PDI (0.498 ± 0.1), ZP (-16.2 ± 0.3), and %EE of NCM and ERL (50.04 ± 2.8 and 05.42 ± 1.3). In vitro release studies indicated the controlled release of the drugs loaded liposomes (87.06 ± 9.93% and 42.33 ± 0.89% in 24 h).