目的：为治疗大鼠缺血性心律失常，构建抗体修饰的脂质体，递送AMO-1到缺血心肌。方法采用薄膜分散法制备脂质体，并分析脂质体的粒径、电位、包封率和释放率，用流式细胞仪评价心肌细胞对脂质体的摄取，小动物活体成像评价脂质体在大鼠体内的靶向性，通过细胞毒性实验确定给药浓度，采用心电图评价cT-A-LIP抗心律失常作用。结果脂质体的粒径均小于120 nm，电位大于-3.8 mV，包封率为（63.0±5.7）%，24 h累积释放率为（32.6±0.7）%。流式细胞仪结果显示，心肌细胞对A-LIP、cT-A-LIP都有一定的摄取率，但有一定差异。小动物活体成像结果显示，cT-A-LIP组药物靶向心脏缺血部位。细胞毒性实验结果显示，脂质体中0.5μmol/L的AMO-1浓度是cT-A-LIP和A-LIP的最大有效安全剂量。心电图结果显示，给药24 h后ST段明显下降并接近于正常水平。结论抗cTnI抗体修饰AMO-1脂质体能够靶向到大鼠的缺血心肌，并且能够缓解缺血性心率失常。%Objective To construct an antibody modified liposome to deliver AMO-1 to ischemic myocardium for ar-rhythmia therapy in rats. Methods The liposomes were prepared by the thin film hydration process. The particle size, zeta potential, encapsulation efficiency and release rate of liposomes were analyzed. The uptake of liposomes by primary myocardial cells was evaluation by flow cytometry. The targeting distribution of liposomes was monitored by the in vivo imaging. The concentration of the drug was determined by the cytotoxicity test. The anti-arrhythmic effects of cT-A-LIP were evaluated by electrocardiograms (ECG). Results The size of liposomes was less than 120 nm, the potential was higher than-3.8 mV, the encapsulation efficiency was (63.0±5.7)%, and the cumulative release rate after 24 hours was (32.6±0.7)%. The results of flow cytometry showed that cT-A-LIP and A-LIP were internalized by primary my-ocardial cells to some extent, and there were significant differences. The data from the in vivo imaging showed that the drug was accumulated to the foci in the heart. The results of cell toxicity test showed that 0.5 μmol/L AMO-1 concen-tration in the liposome was the largest safe and effective dose of cT-A-LIP and A-LIP. ECG results showed that the ST segment was obviously decreased and close to the normal level at 24 hours after drug administration. Conclusion The liposomes modified with anti-cTnI antibody as AMO-1 carriers are able to target ischemic myocardium in rats and relieve ischemic arrhythmias.
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