摘要
为了提高难溶性药物的溶出及生物利用度,采用有序介孔有机硅(PMOs)构建新型药物递送系统。研究以1,2-二(三乙氧基硅基)乙烷(BTEE)为桥联有机硅源,采用水热合成法制备PMOs载体,并负载难溶性药物非诺贝特(1)制得1/PMOs。随后考察了载体结构、药物的体外溶出和体内生物利用度等。结果显示,PMOs为孔径均一的介孔材料(孔径为3.65 nm),孔壁为含有乙烷基的有机-无机杂化的无定型结构。与1原料药相比,1/PMOs能显著提高药物的体外溶出速率,5 min溶出率能达到90%以上。大鼠体内药动学显示,1/PMOs的相对生物利用度是1混悬液的8倍。这是因为载体的比表面积大,药物高度分散并物理吸附于有序介孔孔道中,并因孔道的限制而呈水溶性的无定型状态,从而加快了在胃肠道中的溶出速率,提高了体内吸收,有效解决1口服生物利用度低的问题。
To improve the dissolution and bioavailability of poorly soluble drugs,a novel drug delivery system based on periodic mesoporous organosilicas(PMOs)was proposed.The PMOs carriers were synthesized via a hydrothermal method using 1,2-bis(triethoxysilyl)ethane(BTEE)as the bridged organosilica precursor.The poorly soluble drug fenofibrate(1)was loaded onto the carriers to obtain the drug delivery system,1/PMOs.The the carrier structure,in vitro dissolution and in vivo bioavailability of the drug were investigated.The results showed that the PMOs exhibited a uniform mesoporous structure with a pore size of 3.65 nm,and the pore walls were composed of an organic-inorganic hybrid amorphous framework containing ethane groups.Compared with the bulk drug 1,1/PMOs significantly increased the in vitro dissolution rate of drug,achieving over 90%dissolution within 5 min.In vivo pharmacokinetic studies in rats demonstrated that the relative bioavailability of 1/PMOs was increased to 800%of that of the 1 suspension.This enhancement could be attributed to the high specific surface area of the carrier,which allowed the drug to be highly dispersed and physically adsorbed within the ordered mesopores.Due to the limitations of the pore channels,the drug remained in a water-soluble amorphous state,thereby accelerating its dissolution in the gastrointestinal tract and improving its in vivo absorption.This strategy effectively solves the low oral bioavailability of 1.
作者
吕江维
张伊佳
梁喜龙
张文君
曲有鹏
LYU Jiangwei;ZHANG Yijia;LIANG Xilong;ZHANG Wenjun;QU Youpeng(School of Pharmacy,Harbin University of Commerce,Harbin 150076;Beijing Hainuokang Pharmaceutical Trading Co.,Ltd.,Beijing 102200;School of Life Science and Technology,Harbin Institute of Technology,Harbin 150080)
出处
《中国医药工业杂志》
2025年第12期1545-1552,1575,共9页
Chinese Journal of Pharmaceuticals
基金
黑龙江省中医药管理局中医药科研课题项目(ZHY2025-073)
国家重点研发计划子课题项目(2022YFD1600502-23)
2023年度新一轮黑龙江省“双一流”学科协同创新成果项目(LJGXCG2023-101)。
关键词
有序介孔有机硅
非诺贝特
降血脂药
溶出度
生物利用度
药物递送系统
药代动力学
periodic mesoporous organosilica
fenofibrate
lipid-lowering drug
dissolution
bioavailability
drug delivery system
pharmacokinetics
