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目的 制备三苯基膦阳离子(TPP)和心肌归巢肽(CHP)双修饰葛根素脂质体(PUE@T/C-Lp)，并考察其减少心肌缺血/再灌注(I/R)损伤的作用。方法 合成TPP修饰的聚乙二醇-聚乙烯(TPP-PEG-PE)和CHP修饰的聚乙二醇-聚乙烯(CHP-PEG-PE)，以磷脂与药物用量比、TPP-PEG-PE和CHP-PEG-PE用量作为主要因素，采用Box-Behnken设计-响应面法优化PUE@T/C-Lp处方，测定包封率、载药量、粒径和Zeta电位，透射电子显微镜观察外观形态，考察其稳定性和体外释放特性。基于心肌I/R损伤小鼠模型，评价PUE@T/C-Lp抑制缺血心肌细胞凋亡、减少心肌I/R损伤的效果。结果 优选后的PUE@T/C-Lp呈规则圆球形结构，粒径和Zeta电位表现出良好的正态分布，其包封率和载药量分别为(84.2±0.2)%和(5.8±0.3)%，体外放置稳定，呈明显缓释特征。动物实验结果表明，PUE@T/C-Lp相较其他对照组，能显著减少心肌I/R组织受损程度，降低心肌细胞凋亡率，减轻缺血心肌线粒体损伤及降低活性氧水平。结论 基于Box-Behnken设计-响应面法优化得到的PUE@T/C-Lp具有较高的包封率和载药量，能显著增强葛根素抑制缺血心肌细胞凋亡的作用，减少心肌I/R损伤。
Abstract：Objective To prepare triphenylphosphonium bromide cation (TPP) and cardiac homing peptide (CHP) dual-modified puerarin liposomes (PUE@T/C-Lp) and to determine its effects on reducing myocardial ischemia/reperfusion (I/R) injury.Methods TPP modified polyethylene glycol-polyethylene (TPP-PEG-PE) and CHP modified polyethylene glycol-polyethylene (CHP-PEG-PE) were synthesized.With drug-to-lipid ratio,TPP-PEG-PE and CHP-PEG-PE amounts as the key factors,the formulation was optimized by Box-Behnken design-response surface methodology.The optimized PUE@T/C-Lp was characterized for encapsulation efficiency (EE%),drug loading (DL%),particle size,and Zeta potential.The morphological characterization was observed by transmission electron microscopy,while the stability and in vitro release characteristics were determined.Based on the mouse model of myocardial I/R injury,the effect of PUE@T/C-Lp on inhibiting the apoptosis of ischemic cardiomyocytes and reducing myocardial I/R injury was evaluated.Results The optimized PUE@T/C-Lp had spherical morphology with narrow size distribution and favorable Zeta potential.Its encapsulation efficiency and drug loading capacity were (84.2±0.2)% and (5.8±0.3)%,respectively,and were stable for in vitro placement with obvious slow release characteristics.In vivo studies showed that PUE@T/C-Lp greatly reduced the degree of damage to the myocardial I/R tissues,lowered the rate of cardiomyocyte apoptosis,and reduced the ischemic myocardial mitochondrial damage and ROS levels compared with those of other control groups.Conclusion The optimized PUE@T/C-Lp based on Box-Behnken design-response surface methodology exhibited a high encapsulation rate and drug loading capacity,which obviously enhanced the inhibition of apoptosis of ischemic cardiomyocytes and reduced the myocardial I/R injury.
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基本信息:
DOI：
中图分类号:R285.5
引用信息:
[1]胡雄彬,唐甜甜,向大雄,等.基于Box-Behnken设计-响应面法优选TPP/CHP双修饰葛根素脂质体及其对心肌缺血/再灌注损伤的作用[J].中南药学,2025,23(09):2487-2494.
基金信息:
湖南省自然科学基金项目(No.2024JJ8126,No.2020JJ4128,No.2025JJ80100); 湖南省卫健委项目(No.W20243065); 长沙市自然科学基金(No.kq2403088); 中南大学研究生教育教学改革项目(No.2024JGB158,No.2025YJSKS038)