血根碱壳聚糖微球的制备工艺优化及体内外性能研究  

Preparation Process Optimization and in Vitro and in Vivo Properties of Sanguinarine Chitosan Microspheres

作　　者：李春梅 史彤辉 陈旭 张馨元 周长胜 LI Chunmei;SHI Tonghui;CHEN Xu;ZHANG Xinyuan;ZHOU Changsheng(School of Pharmacy,Harbin University of Commerce,Harbin 150076,China;Beijing Kexin Jurun Pharmaceutical Technology Co.,Ltd.,Harbin 150000,China;College of Marxism,Harbin University of Commerce,Harbin 150028,China)

机构地区：[1]哈尔滨商业大学药学院,黑龙江哈尔滨150076 [2]北京科信聚润医药科技有限公司哈尔滨分公司,黑龙江哈尔滨150000 [3]哈尔滨商业大学马克思主义院,黑龙江哈尔滨150028

出　　处：《特产研究》2024年第2期36-46,共11页Special Wild Economic Animal and Plant Research

基　　金：黑龙江省哲学社会科学研究规划项目(21KSE330);2023年度黑龙江省中医药经典普及化专项项目(ZYW2023-077);2023年度黑龙江省博士后科研启动金项目(BS0051)。

摘　　要：本研究旨在探讨血根碱壳聚糖微球的最优制备方法,并对微球进行外观粒径表征和体内外研究。本研究建立了血根碱含量测定的HPLC法,运用乳化交联法制备血根碱壳聚糖微球,以载药量、包封率和平均粒径为评价指标,应用单因素试验和星点设计-响应面法优化制备处方。利用显微镜和扫描电镜观察微球外观形态,通过激光粒度仪测定微球粒径及其分布。采用动态透析法取不同时间点的血根碱原料药溶液和血根碱壳聚糖微球溶液,并考察两种溶液的体外释放度,最后进行药动学方程拟合。对不同组小鼠注射血根碱原料液和血根碱微球液,不同时间取组织血测定,观察体内分布及靶向性。结果表明:血根碱HPLC含量测定得曲线方程y=2.530 0x+43.323 1(R^(2)=0.999 8,线性范围为10.0~50.0μg/mL)。单因素试验和星点设计-响应面法得最优处方:血根碱投药量60 mg,壳聚糖用量70mg,乳化剂用量5%,戊二醇用量0.25mL、水油体积比3:10,醋酸浓度2%、搅拌速度500r/min和交联时间3.5h。观察到血根碱壳聚糖微球形态近似球形及表面较光滑,测定得平均粒径(8.17±0.16)μm,粒径分布为2~20μm。体外释放显示,血根碱壳聚糖微球较血根碱原料药释放缓慢,Ritger-Peppas方程拟合效果较好(R^(2)=0.980 8)。血根碱微球在小鼠体内有明显缓释作用,在肺部和肝脏存在不同程度靶向性。血根碱壳聚糖微球体外释放具有明显的缓释作用,在小鼠体内分布具有一定靶向性和缓释性。To investigate the optimal preparation of sanguinarine chitosan microspheres,and and to characterize the appearance and particle size of the microspheres and study them in vitro and in vivo.An HPLC method for the determination of sanguinarine was established.Sanguinarine chitosan microspheres were prepared by emulsion crosslinking method.The formulation was optimized by single factor test and central composite design response surface method with drug loading,encapsulation efficiency and average particle size as evaluation indicators.The appearance and morphology of microspheres were observed by microscope and scanning electron microscope,and the particle size and distribution of microspheres were determined by laser particle sizer.Sanguinarine bulk drug solution and sanguinarine chitosan microspheres solution at different time points were obtained by dynamic dialysis method,and the in vitro release rates of the two solutions were investigated.Finally,the pharmacokinetic equation was fitted.Different groups of mice were injected with sanguinarine raw material solution and sanguinarine microsphere solution,and tissue blood was taken at different times for determination to observe the distribution and targeting in vivo.The curve equation of sanguinarine HPLC was y=2.5300x+43.3231(R^(2)=0.9998,linear range 10.0~50.0 g/mL).The optimal formula was obtained by single factor test and central composite design response surface method:sanguinarine dosage 60 mg,chitosan dosage 70 mg,emulsifier dosage 5%,pentanediol dosage 0.25mL,water oil volume ratio 3:10,acetic acid concentration 2%,stirring speed 500 r/min and crosslinking time 3.5 h.The morphology of sanguinarine chitosan microspheres was observed to be nearly spherical and the surface was smooth,and the average particle size was determined to be(8.17±0.16)m,with the particle size distribution ranging from 2 to 20 m.In vitro release showed that sanguinarine chitosan microspheres were released more slowly than haematoxylin API,and the Ritger-Peppas equation fitted better

关 键 词：血根碱 微球 星点设计-响应面法 体外释放 缓释 靶向性 

分 类 号：R943[医药卫生—药剂学] R965[医药卫生—药学]