董欣,刘阳,温梦,王浩,程博闻
DONG Xin,WEN Meng,LIU Yang,WANG Hao,CHENG Bowen

• 1:锦州医科大学药学院
• 2:山东省医学科学院药物研究所
• 3:天津科技大学化学工程与材料科学学院

摘要(Abstract)：

目的 考察Poloxamer188聚D,L-乳酸-co-乙醇酸电纺纤维中阿那曲唑的释放行为及家兔口服药物动力学。方法 采用均相溶液静电纺丝法制备载药电纺纤维，扫描电子显微镜法考察纤维形态，X-射线衍射和红外光谱考察纤维中材料复合和载药行为。高效液相色谱-紫外分光光度法考察载药纤维体外释放行为和家兔口服后血浆药物质量浓度经时曲线。结果 相对于聚D,L-乳酸-co-乙醇酸的质量百分比，当Poloxamer188复合量为12.5%和阿那曲唑载药量为10%、20%和30%时，可以得到澄清的待纺溶液，静电纺丝能够进行，且纤维形态良好。随着阿那曲唑载量的增高，3 d后药物的释放百分量逐渐降低，所有纤维在1 d后药物百分释放量均大于70%。口服结果表明相比于固体分散体，载药纤维的相对生物利用度为前者的76.2%,最大血药质量浓度为前者的38.3%。结论 Poloxamer188复合聚D,L-乳酸-co-乙醇酸电纺纤维可以作为阿那曲唑每日单次口服缓释载体进行进一步的开发。
Objective To investigate the release behavior and the pharmacokinetics of oral administration in rabbits of anastrozole incorporated in Poloxamer188 complexed poly D,L-lactic acid-co-glycolic acid electrospun fibers.Methods The drug-incorporated electrospun fibers were prepared by homogeneous solution electrospinning.Morphology of fibers was observed by scanning electron microscope.Materials complexing and drug incorporating within fibers were investigated by X-ray diffraction and infrared spectrum.High performance liquid chromatography-ultraviolet spectrophotometer was used to investigate the release behavior of drug-incorporated fibers in vitro and the plasma drug concentration-time curve of rabbits after oral administration.Results When Poloxamer188 complexing amount was 12.5% and anastrozole incorporating amounts was 10%,20%,30% relative to poly D,L-lactic acid-co-glycolic acid in mass ratio, transparent solutions could be obtained for electrospinning which went on smoothly to produce fibers with desirable morphology.As anastrozole incorporating amounts increased, the percentages of its release amounts decreased gradually along with after 3 days.Percentage release amounts of all fibers were more than 70% after 1 day.Results of oral administration presented that the relative bioavailability of drug-incorporated fibers was 76.2% to that of solid dispersion and the maximum blood concentration was 38.3% to that of solid dispersion.Conclusion Poloxamer188 complexed poly D,L-lactic acid-co-glycolic acid electrospun fibers could be further developed as a sustained-release carrier for daily single oral administration of anastrozole.

关键词(KeyWords)： 阿那曲唑;纤维;静电纺丝;Poloxamer188;聚乳酸-co-乙醇酸;缓释
anastrozole;fiber;electrospinning;Poloxamer188;poly lactic acid-co-glycolic acid;sustained release

Abstract:

Keywords:

基金项目(Foundation): 辽宁省药物作用与质量评价专业技术创新中心与辽宁省海洋生物活性物质重点实验室主任基金资助项目(2020-06);; 辽宁省药物作用与质量评价工程技术研究中心主任基金资助项目(2018110605);; 国家自然科学基金资助项目(51673148)

作者(Author): 董欣,刘阳,温梦,王浩,程博闻
DONG Xin,WEN Meng,LIU Yang,WANG Hao,CHENG Bowen

DOI: 10.14066/j.cnki.cn21-1349/r.2021.0132

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