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声学微泡是近年发展起来的药物靶向递送系统,利用超声波作用促进药物或基因定位释放到细胞或组织中。本文利用星点设计(CCD)结合效应面法(RSM)优化声学脂质微泡制备条件。蛋黄磷脂、Tween 80和聚乙二醇1500是影响2～8μm微泡浓度的主要因素。本文应用星点设计综合考察这些因素,利用效应面优化法得到最佳处方。实验评价指标为2～8μm粒径的微泡浓度。采用多元二次方程对实验结果进行拟合,从而产生三维效应曲面图,最佳处方条件可从三维效应曲面的顶点得到。优化实验得到的最佳处方进行加速试验,考察稳定性。通过体内造影效果实验,研究本品的声学效应,并与国外上市产品SonoVue(进行对照。结果表明,3个考察因素对2～8μm微泡浓度均有影响,最佳处方配比为:蛋黄磷脂8.35mg,Tween8021.68mg和聚乙二醇1500201mg。所制备的2～8μm微泡浓度平均值达到8.60×109.mL-1。加速试验结果显示脂质微泡物理稳定性良好。本品最佳处方体内造影强度(相对强度)和持续时间分别为4.47±0.15和(302±7)s,与国外上市产品SonoVue([4.28±0.13和(309±8)s]无明显差异。星点设计结合效应面法筛选出的声学脂质微泡浓度高,物理稳定性和声学造影效果好。
Acoustical microbubbles are drug-targeted delivery systems developed in recent years that use ultrasound to facilitate the release of drugs or genes into cells or tissues. In this paper, we optimized the preparation conditions of acoustic lipid microbubbles by the combination of star design (CCD) and response surface methodology (RSM). Egg yolk phospholipid, Tween 80 and polyethylene glycol 1500 are the main factors affecting the concentration of 2-8μm microbubbles. In this paper, the star point design comprehensive study of these factors, the use of response surface optimization method to get the best prescription. Experimental evaluation indicators for the 2 ~ 8μm particle size microbubble concentration. The multivariate quadratic equation was used to fit the experimental results to generate the three-dimensional effect surface map. The optimal prescription conditions were obtained from the vertices of the three-dimensional effect surface. Optimize the experiment to get the best prescription for accelerated testing, investigate the stability. Through the in vivo contrast effect experiment, the acoustical effect of this product was studied and compared with the foreign product SonoVue (control. The results showed that all the three factors had an effect on the concentration of 2 ~ 8μm microbubbles. The optimal prescription ratio was: 8.35mg, Tween8021.68mg and polyethylene glycol 1500201mg. The average concentration of 2-8μm microbubbles prepared reached 8.60 × 109.mL-1 accelerated test results show that the physical stability of lipid microbubbles is good. The contrast intensity and duration were 4.47 ± 0.15 and (302 ± 7) s respectively in the prescription, which showed no significant difference with SonoVue ([4.28 ± 0.13 and (309 ± 8) s] Response surface method to filter out the high concentration of acoustic lipid microbubbles, physical stability and acoustic contrast effect.