目的验证脂质体药物在心肌缺血区域的炎症靶向效应,探讨其减少心肌细胞缺血再灌注损伤的治疗优势。方法采用薄膜分散-超声-膜挤出法制备胺碘酮及丙酮酸乙酯(EP)脂质体,并对其进行粒径、包封率检查。通过阻断和恢复冠状动脉血流制备大鼠...目的验证脂质体药物在心肌缺血区域的炎症靶向效应,探讨其减少心肌细胞缺血再灌注损伤的治疗优势。方法采用薄膜分散-超声-膜挤出法制备胺碘酮及丙酮酸乙酯(EP)脂质体,并对其进行粒径、包封率检查。通过阻断和恢复冠状动脉血流制备大鼠心肌缺血再灌注损伤(MI-RI)模型,并通过缺血再灌注(I-R)前后心电图变化验证模型。尾静脉给药,考察荧光脂质体在I-R心肌中的炎症靶向效性;取24只SD大鼠(随机分为4组,每组6只),考察胺碘酮脂质体对MI-RI心律失常事件的影响;另取24只SD大鼠(随机分为4组,每组6只),评估丙酮酸乙酯(EP)脂质体对MI-RI中凋亡蛋白Bax,Bcl-2和caspase-3表达水平的影响。结果制备的脂质体药物粒径均匀,制备后24 h内药物渗漏不高于18%。在大鼠心肌I-R后可见心电图ST段及T波的缺血性动态演变,再灌注后心电图记录到了室性心动过速事件,其中I-R+胺碘酮脂质体组心律失常评分明显降低,(P<0.01),且低于胺碘酮溶液组(1.5±0.96 vs 3.0±0.82,P<0.05)。离体荧光成像显示,I-R+IR-775脂质体组荧光强度最高,即荧光脂质体药物可以靶向聚集到心肌缺血部位。与I-R+空白脂质体组和I-R+EP溶液组相比,I-R+EP脂质体组在48 h后显著降低了Bax和caspase-3蛋白表达水平,提高了Bcl-2蛋白的表达,Bax/Bcl-2比值明显下降(P<0.05)。结论脂质体药物在MI-RI中具有显著的炎症靶向效应,脂质体载药结构增强了胺碘酮和EP对MI-RI的治疗效果。展开更多
Liposomes were prepared with natural soybean phospholipids by extrusion method after rotating-film evaporating technique. Transmission electron micrography was used to detect the appearances of the prepared liposomes,...Liposomes were prepared with natural soybean phospholipids by extrusion method after rotating-film evaporating technique. Transmission electron micrography was used to detect the appearances of the prepared liposomes, and the liposome diameter was also measured. The prepared liposomes were sphere in shape with the mean diameter of 217 nm and span of 0.838. The phospholipid bilayer structure, suitable for entrapping various effector molecules, could be seen clearly under transmission electron microscopy. The bile salts of sodium cholate and sodium deoxycholate were used as the surfactants to investigate their interaction with liposomes. The turbidities for the mixture of bile salts and liposomes were evaluated by the visible spectrometry method at the wavelength of 500 nm. And the diameter changes of liposomes were also tested to examine the effect of bile salts on liposomes. At the beginning, the diameters and turbidities of liposomes increased a little as the result of mixed micelles formation during the different stages for the structure changes of surfactant-liposomes micelles. The further added bile salts decreased the diameters and turbidities of liposomes. The liposome suspension underwent several rearrangements before small mixed micelles formed. And the diameter of liposomes changed regularly. The interaction of bile salts and liposomes is important for the further study of the behaviors of liposomes in vivo. The drug loaded and release properties of liposomes can also be well reflected by the interaction of liposomes and surfactants.展开更多
Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipi...Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers（NLCs） were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency（EE） and percentage of drug loading（DL） of ART-NLC were（53.06±2.11） nm,（–28.7±3.59） m V, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection（i.v） or intraperitoneal injection（i.p） were investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞（（707.45±145.65） ng·h/m L） of ART-NLC were significantly bigger than that of ART（（368.98±139.58） ng·h/m L）. The MRT（（3.38±0.46） h） of ART-NLC was longer than that of ART（（1.39±0.61） h）. And similar results were observed for rats of i.p groups. The AUC0–∞（（1233.06±235.57） ng·h/m L） and MRT（（4.97±0.69） h） of ART-NLC were both bigger than those of ART, which were（871.17±234.03） ng·h/m L） and（1.75±0.31） h）, respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞（P〈0.05） and MRT（P〈0.001） for both i.p and tail i.v administrations.展开更多
文摘目的验证脂质体药物在心肌缺血区域的炎症靶向效应,探讨其减少心肌细胞缺血再灌注损伤的治疗优势。方法采用薄膜分散-超声-膜挤出法制备胺碘酮及丙酮酸乙酯(EP)脂质体,并对其进行粒径、包封率检查。通过阻断和恢复冠状动脉血流制备大鼠心肌缺血再灌注损伤(MI-RI)模型,并通过缺血再灌注(I-R)前后心电图变化验证模型。尾静脉给药,考察荧光脂质体在I-R心肌中的炎症靶向效性;取24只SD大鼠(随机分为4组,每组6只),考察胺碘酮脂质体对MI-RI心律失常事件的影响;另取24只SD大鼠(随机分为4组,每组6只),评估丙酮酸乙酯(EP)脂质体对MI-RI中凋亡蛋白Bax,Bcl-2和caspase-3表达水平的影响。结果制备的脂质体药物粒径均匀,制备后24 h内药物渗漏不高于18%。在大鼠心肌I-R后可见心电图ST段及T波的缺血性动态演变,再灌注后心电图记录到了室性心动过速事件,其中I-R+胺碘酮脂质体组心律失常评分明显降低,(P<0.01),且低于胺碘酮溶液组(1.5±0.96 vs 3.0±0.82,P<0.05)。离体荧光成像显示,I-R+IR-775脂质体组荧光强度最高,即荧光脂质体药物可以靶向聚集到心肌缺血部位。与I-R+空白脂质体组和I-R+EP溶液组相比,I-R+EP脂质体组在48 h后显著降低了Bax和caspase-3蛋白表达水平,提高了Bcl-2蛋白的表达,Bax/Bcl-2比值明显下降(P<0.05)。结论脂质体药物在MI-RI中具有显著的炎症靶向效应,脂质体载药结构增强了胺碘酮和EP对MI-RI的治疗效果。
文摘Liposomes were prepared with natural soybean phospholipids by extrusion method after rotating-film evaporating technique. Transmission electron micrography was used to detect the appearances of the prepared liposomes, and the liposome diameter was also measured. The prepared liposomes were sphere in shape with the mean diameter of 217 nm and span of 0.838. The phospholipid bilayer structure, suitable for entrapping various effector molecules, could be seen clearly under transmission electron microscopy. The bile salts of sodium cholate and sodium deoxycholate were used as the surfactants to investigate their interaction with liposomes. The turbidities for the mixture of bile salts and liposomes were evaluated by the visible spectrometry method at the wavelength of 500 nm. And the diameter changes of liposomes were also tested to examine the effect of bile salts on liposomes. At the beginning, the diameters and turbidities of liposomes increased a little as the result of mixed micelles formation during the different stages for the structure changes of surfactant-liposomes micelles. The further added bile salts decreased the diameters and turbidities of liposomes. The liposome suspension underwent several rearrangements before small mixed micelles formed. And the diameter of liposomes changed regularly. The interaction of bile salts and liposomes is important for the further study of the behaviors of liposomes in vivo. The drug loaded and release properties of liposomes can also be well reflected by the interaction of liposomes and surfactants.
基金National Natural Science Foundation of China(Grant No.81373364)The Subject clots Project Serving Pharmaceutical Industrial Innovation of Shanxi Province
文摘Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers（NLCs） were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency（EE） and percentage of drug loading（DL） of ART-NLC were（53.06±2.11） nm,（–28.7±3.59） m V, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection（i.v） or intraperitoneal injection（i.p） were investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞（（707.45±145.65） ng·h/m L） of ART-NLC were significantly bigger than that of ART（（368.98±139.58） ng·h/m L）. The MRT（（3.38±0.46） h） of ART-NLC was longer than that of ART（（1.39±0.61） h）. And similar results were observed for rats of i.p groups. The AUC0–∞（（1233.06±235.57） ng·h/m L） and MRT（（4.97±0.69） h） of ART-NLC were both bigger than those of ART, which were（871.17±234.03） ng·h/m L） and（1.75±0.31） h）, respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞（P〈0.05） and MRT（P〈0.001） for both i.p and tail i.v administrations.
