磷脂种类对吲哚菁绿脂质体制剂学性质的影响  

Impact of phospholipid type on pharmaceutical characteristics of indocyanine green liposomes

作　　者：廉唱唱 周梅 彭成军 汪永忠 桂双英 李真宝 LIAN Changchang;ZHOU Mei;PENG Chengjun;WANG Yongzhong;GUI Shuangying;LI Zhenbao(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;Institute of Pharmaceutics,Anhui Academy of Chinese Medicine,Hefei 230012,China;Anhui Key Laboratory of Pharmaceutical Preparation Technology and Application,Hefei 230012,China;Engineering Technology Research Center of Modern Pharmaceutical Preparation,Anhui Province,Hefei 230012,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230012 [2]安徽省中医药研究院药物研究所,安徽合肥230012 [3]药物制剂技术与应用安徽省重点实验室,安徽合肥230012 [4]安徽省现代药物制剂工程技术研究中心,安徽合肥230012

出　　处：《药物评价研究》2023年第3期524-530,共7页Drug Evaluation Research

基　　金：国家自然科学基金项目(82003675);安徽中医药大学培育项目(2020py04,2021py05);安徽省高校科学研究项目(KJ2020A0429)。

摘　　要：目的探究磷脂种类对吲哚菁绿(ICG)脂质体制剂学性质的影响。方法采用薄膜水化挤出法分别制备以氢化大豆卵磷脂(HSPC)、蛋黄卵磷脂为脂质成分的脂质体(ICG-H-Lipo、ICG-E-Lipo)。采用Zetasizer3000HS粒径仪测定脂质体的粒径、聚合物分散性指数(PDI)和Zeta电位;透射电子显微镜观察脂质体形态;超滤离心法分别测定ICG-H-Lipo和ICG-E-Lipo的包封率。用紫外分光光度计分别测定ICG-E-Lipo、ICG-H-Lipo及游离ICG在400~1000 nm的紫外吸收光谱。以粒径变化为指标,考察脂质体用纯水稀释10倍、4℃条件下储存1个月的长期稳定性,考察脂质体在模拟血浆(pH 7.4大鼠血浆)中的稳定性,考察脂质体用纯水稀释10倍后给予808 nm激光辐照(1 w·cm^(−2)、5 min)7 d内稳定性;将ICG-HLipo、ICG-E-Lipo和游离ICG 4℃避光保存,分别于0、1、3、5、7 d检测ICG在780 nm处的吸光度(A)值。将ICG-ELipo、ICG-H-Lipo和游离ICG配制成ICG质量浓度为25μg·mL^(−1)的溶液,给予1 w·cm^(−2)、808 nm激光辐照5 min,用红外热像仪记录温度变化;给予5个808 nm激光开-关辐照(1 w·cm^(−2),开5 min,关15 min),用红外热成像仪记录温度变化;采用1 w·cm^(−2)、808 nm激光分别辐照0、1、2、3、4 min,用紫外分光光度计检测A值变化;以评价不同制剂的光热效率。结果成功制备了ICG-H-Lipo和ICG-E-Lipo,粒径分布均匀,ICG的包封率分别为77.97%和70.67%。ICG-E-Lipo、ICG-H-Lipo均在895 nm处出现了强吸收峰,相比于游离ICG,ICG-E-Lipo、ICG-H-Lipo均发生了明显红移。稳定性结果表明,ICG-H-Lipo和ICG-E-Lipo在去离子水、血浆溶液中及激光照射后粒径没有明显变化;储存7 d后的紫外吸收光谱图显示,ICG-E-Lipo和ICG-H-Lipo具有比游离ICG更好的稳定性(P<0.05、0.001),且ICG-H-Lipo中的ICG稳定性最好。经过808 nm激光辐照5 min后,ICG-E-Lipo、ICG-H-Lipo、游离ICG的温度均能达到肿瘤细胞的死亡温度;在5次激光开-关循环照射后,Objective To investigate the impact of phospholipid type on the pharmacological properties of indocyanine green(ICG)liposomes.Methods Liposomes(ICG-H-Lipo,ICG-E-Lipo)with hydrogenated soybean lecithin(HSPC)and egg yolk lecithin as lipid components were prepared by thin film hydration extrusion method.The particle size,polymer dispersion index(PDI)and Zeta potential of liposomes were measured by Zetasizer3000HS particle size analyzer.The morphology of liposomes was observed by transmission electron microscopy.The encapsulation efficiency of ICG-H-Lipo and ICG-E-Lipo were determined by ultrafiltration centrifugation.The ultraviolet absorption spectra of ICG-E-Lipo,ICG-H-Lipo and free ICG in the range of 400—1000 nm were determined by ultraviolet spectrophotometer.With the change of particle size as an index,the long-term stability of liposomes diluted with 10 times pure water and stored at 4℃for 1 month was investigated,the stability of liposomes in simulated plasma(pH 7.4 rat plasma)was investigated,and the stability of liposomes diluted with 10 times pure water and irradiated with 808 nm laser(1 w·cm^(−2),5 min)within seven days was investigated.ICG-H-Lipo,ICG-E-Lipo and free ICG were stored in dark at 4℃,and the absorbance(A)value of ICG at 780 nm was measured at 0,1,3,5 and 7 days respectively.In order to evaluate the photothermal efficiency of different preparations,ICG-E-Lipo,ICG-H-Lipo and free ICG were prepared into ICG with a mass concentration of 25μg·mL^(−1) solution,irradiated with 1 w·cm^(−2),808 nm laser for 5 min,and recorded the temperature change with infrared thermal imager.Give five 808 nm laser on-off irradiation(1 w·cm^(−2),on 5 min,off 15 min),and record the temperature change with infrared thermal imager.Irradiate 1 w·cm^(−2)and 808 nm laser for 0,1,2,3 and 4 min respectively,and detect the change of A value with ultraviolet spectrophotometer.Results ICG-H-Lipo and ICG-E-Lipo liposomes were successfully prepared by the thin film hydration and extrusion method,the ICG enc

关 键 词：吲哚菁绿 脂质体 氢化大豆卵磷脂 蛋黄卵磷脂 稳定性 光热效率 

分 类 号：R943[医药卫生—药剂学]