超声介导载和厚朴酚超声微泡的制备与体内评价

Preparation and in vivo evaluation of honokiol loaded ultrasound microbubble

目的研究超声介导载和厚朴酚超声微泡的体外性质以及对小鼠H22皮下移植瘤的抑制效果。方法采用机械震荡法制备具有超声响应击破特性的和厚朴酚超声微泡,使用星点效应面法对其处方进行优化。检测其一般性质,包括载药率、包封率、体外释药性能、显影性能等。建立小鼠H22皮下移植瘤模型,将荷瘤小鼠随机分为给药组和对照组,隔日治疗1次,连续治疗7 d后,绘制各组小鼠的肿瘤生长曲线并计算肿瘤生长抑制率。结果优化处方制备的和厚朴酚超声微泡载药率为(1.09±0.40)%,包封率为(74.02±3.61)%,平均粒径为(308.6±35.2)nm,水囊实验微泡呈现良好的超声显影特性。治疗期间,对照组的肿瘤体积增长较快,而超声介导载和厚朴酚超声微泡组小鼠肿瘤增长最为缓慢。与超声处置空白微泡组相比,超声介导载和厚朴酚超声微泡组小鼠的肿瘤质量显著减小,具有统计学差异。结论超声响应和厚朴酚微泡可抑制小鼠H22皮下移植瘤的生长,在药物靶向递送方面展现出良好应用前景。

Objective To determine the in vitro characteristics of honokiol loaded ultrasound microbubbles as well as their inhibitory effect on the H22 subcutaneous transplantation tumor in mice.Methods Mechanical shock method was used to prepare the honokiol ultrasound microbubbles.The response surface methodology was used to optimize the prescription.General properties were detected,including the loading capacity of drug,the encapsulation efficiency of drug,in vitro drug release performance and ultrasonic imaging.The H22 subcutaneous implanted tumor mouse model was established.The implanted mice were randomly divided into an administration group and a control group.The mice were treated every other day for consecutive 7 days.The tumor growth curve of each group was obtained and the tumor growth inhibition rate was calculated.Results The optimized prescription of honokiol ultrasound microbubbled was obtained.The loading capacity of drug was(1.09±0.40)%,the encapsulation efficiency was(74.02±3.61)%,and the average particle size was(308.6±35.2)nm.During the treatment,the tumor volume of the control group increased rapidly,while the tumor growth of mice in the honokiol ultrasound microbubble group grew slowly.Compared with the blank microbubble group,the weight of tumor in the mice in honokiol ultrasound microbubble group were much smaller.Conclusion Honokiol ultrasound microbubbles can inhibit the growth of H22 subcutaneous tumor,showing good application prospects in drug targeted delivery.