波棱瓜子自组装纳米粒的制备及其肠吸收机制研究  

Preparation and intestinal absorption mechanism of self-assembled nanoparticles of Herpetospermum caudigerum

作　　者：朱煜文 邓翔 陈莉 申宝德 薛玉叶 杭凌宇 袁海龙 ZHU Yu-wen;DENG Xiang;CHEN Li;SHEN Bao-de;XUE Yu-ye;HANG Ling-yu;YUAN Hai-long(Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Department of Pharmacy,Air Force Medical Center,PLA,Air Force Medical University,Beijing 100142,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [2]空军军医大学空军特色医学中心药学部,北京100142

出　　处：《中国中药杂志》2024年第12期3212-3219,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(82174074,81873092)。

摘　　要：该实验采用微沉淀法制备波棱瓜子自组装纳米粒(micro-precipitation self-assembled nanoparticles, MP-SAN),以平均粒径和多分散指数(polydispersity index, PDI)为评价指标进行工艺优化,并对最终工艺的粒径、PDI、Zeta电位和微观结构进行表征。通过大鼠在体单向肠灌流试验考察MP-SAN中去氢双松柏醇(dehydrodiconiferyl alcohol, DA)和波棱甲素(herpetrione, Her)的肠吸收机制。结果表明,优化的工艺参数为搅拌转速800 r·min^(-1),搅拌时间5 min,旋蒸温度40℃。所制得的MP-SAN呈现类球状结构且形态均匀,其平均粒径为(267.63±13.27)nm、PDI为0.062 0±0.043 9、Zeta电位为(-46.18±3.66)mV。DA在回肠段的吸收速率常数(K_(a))和表观吸收系数(P_(app))显著高于空肠段(P<0.05),而Her在回肠段和空肠段的吸收无显著差异。当药物浓度升高时,DA和Her的肠吸收参数呈上升趋势,其中高浓度组MP-SAN中DA的K_(a)和P_(app)显著高于低浓度组(P<0.01)。P-糖蛋白抑制剂维拉帕米的加入并未显著影响DA和Her的肠吸收。而加入吲哚美辛后,MP-SAN中DA和Her的吸收均显著增加(P<0.05),表明DA和Her可能是多药耐药相关蛋白2的底物。In this experiment,the micro-precipitation method was used to prepare self-assembled nanoparticles of Herpetospermum caudigerum Wall.(MP-SAN).The process was optimized using average particle size and polydispersity index(PDI)as evaluation indexes.The mean particle size,PDI,zeta potential,and microstructure of MP-SAN were characterized.The intestinal absorption mechanism of dehydrodiconiferyl alcohol(DA)and herpetrione(Her)in MP-SAN was investigated through single-pass intestinal perfusion in rats.The optimized process parameters for producing MP-SAN were a stirring speed of 800 r·min^(-1),stirring time of 5 min,and rotary evaporation temperature of 40℃.The resulting MP-SAN exhibited a spherical-like structure and uniform morphology,with a mean particle size of(267.63±13.27)nm,a PDI of 0.0620±0.0439,and a zeta potential of(-46.18±3.66)mV.The absorption rate constant(K_(a))and apparent permeability coefficient(P_(app))of DA in the ileal segment were significantly higher than those in the jejunal segment(P<0.05).However,there was no significant difference in the absorption of Her between the ileal and jejunal segments.Intestinal absorption parameters of DA and Her tended to increase with increasing drug concentration.Specifically,the K_(a) and P_(app) of DA in MP-SAN in the high-concentration group were significantly higher than those in the low-concentration group(P<0.01).The addition of verapamil,a P-glycoprotein inhibitor,did not significantly affect the intestinal absorption of DA and Her.However,the absorption of both DA and Her in MP-SAN was significantly increased by the addition of indomethacin(P<0.05),suggesting that DA and Her may be substrates for multidrug resistance-associated protein 2.

关 键 词：波棱瓜子 肠吸收 自组装 纳米粒 单向肠灌流 汤剂 

分 类 号：R29[医药卫生—民族医学]