穿心莲内酯包合物微针的物理性状及肺靶向性研究

Physical Properties and Lung Targeting of Andrographolide Inclusion Compound Microneedles

目的制备穿心莲内酯包合物微针,评价其经皮给药的药物代谢动力学(简称药动学)特点及其肺靶向性。方法采用微模塑法制备微针,以针体形态特征、机械强度和皮肤穿刺性能为指标,考察微针的物理性状;将72只大鼠分为对照组(灌胃穿心莲内酯滴丸溶液)和微针组(微针经皮给药),测定血及肺组织中的药物浓度,计算药动学参数并比较,计算肺相对靶向效率。结果微针呈圆锥形,针体均匀且表面平整,机械强度及皮肤穿刺性能良好。与对照组比较,微针组的半衰期缩短55.10%,达峰时间缩短20.00%,峰浓度增加633.85%,且药-时曲线下面积明显增大,药物平均驻留时间明显延长,肺相对靶向效率为20.46。结论穿心莲内酯包合物微针具有足够的机械强度和皮肤穿刺性能,在皮肤中无蓄积,起效快,且肺靶向性良好,相对生物利用度明显高于口服穿心莲内酯滴丸。

Objective To prepare Andrographolide Inclusion Compound Microneedles,and to evaluate its pharmacokinetics and lung targeting by percutaneous administration of microneedles.Methods The microneedles were prepared by the micromolding method,and the physical properties of microneedles were investigated with the morphological characteristics,mechanical strength and skin puncture ability of the needles as indicators.A total of 72 rats were divided into the control group(intragastric administration of Andrographolide Dropping Pill Solution)and the microneedle group(percutaneous administration of microneedles).The drug concentration in blood and lung tissue were measured,and the pharmacokinetic parameters were calculated and compared,and the relative targeting efficiency to lung was calculated.Results The microneedles were conical,uniform and smooth,with good mechanical strength and skin puncture ability.Compared with those in the control group,the half-life shortened by 55.10%,the peak time shortened by 20.00%,and the peak concentration increased by 633.85% in the microneedle group.The area under the curve increased significantly,the average residence time of the drug was prolonged significantly,and the relative efficiency of lung targeting was 20.46.Conclusion Andrographolide Inclusion Compound Microneedles have sufficient mechanical strength and skin puncture ability without accumulation in the skin,they have the advantages of rapid onset and good lung targeting,and their relative bioavailability is significantly higher than that of Oral Andrographolide Drop Pills.