薯蓣皂苷元白蛋白纳米粒制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of diosgenin albumin nanoparticles

作　　者：董亚楠 柳超 董姣姣 李伟宏 李娜 王风云 DONG Ya-nan;LIU Chao;DONG Jiao-jiao;LI Wei-hong;LI Na;WANG Feng-yun(Henan Vocational College of Applied Technology,Zhengzhou 450042,China;Beijing University Cancer Hospital,Beijing 100142,China;Zhengzhou Shuqing Medical College,Zhengzhou 450064,China)

机构地区：[1]河南应用技术职业学院,河南郑州450042 [2]北京大学肿瘤医院,北京100142 [3]郑州澍青医学高等专科学校,河南郑州450064

出　　处：《中成药》2023年第7期2110-2116,共7页Chinese Traditional Patent Medicine

基　　金：2023年度河南省高等学校重点科研项目(23B320013);河南应用技术职业学院青年骨干教师资助项目(2020-GGJS-Y003)。

摘　　要：目的制备薯蓣皂苷元白蛋白纳米粒,并考察其体内药动学。方法高压均质法制备白蛋白纳米粒,单因素试验优化处方,测定其包封率、载药量、粒径、Zeta电位、溶解度、体外释药,分析其晶型、稳定性。18只大鼠随机分为3组,分别灌胃给予薯蓣皂苷元、物理混合物、薯蓣皂苷元白蛋白纳米粒的0.5%CMC-Na混悬液(30 mg/kg),于0.5、1、2、3、4、6、9、12、18 h采血,HPLC法测定薯蓣皂苷元血药浓度,计算主要药动学参数。结果最佳处方为薯蓣皂苷元用量60 mg,水相pH值8.5,白蛋白用量0.9 g,均质压力135 MPa,均质次数10次,包封率为93.59%,载药量为5.70%,粒径为163.72 nm,Zeta电位为-21.67 mV。白蛋白纳米粒溶解度高于原料药、物理混合物,模拟胃液、模拟肠液中其24 h内累积溶出率高于原料药。薯蓣皂苷元在白蛋白纳米粒中以无定形态存在,6个月内稳定性良好。与原料药、物理混合物比较,白蛋白纳米粒t max缩短(P<0.05),t 1/2延长(P<0.05),C max、AUC 0~t、AUC 0~∞升高(P<0.01);与原料药比较,其相对生物利用度增加至3.77倍。结论白蛋白纳米粒可增加薯蓣皂苷元溶解度,促进其体外释药、体内口服吸收。AIM To prepare diosgenin albumin nanoparticles,and to investigate their in vivo pharmacokinetics.METHODS The albumin nanoparticles were prepared by high-pressure homogenization method,after which single factor test was applied to optimizing the formulation,the encapsulation efficiency,drug loading,particle size,Zeta potential,solubility and in vitro drug release were determined,and the crystalline form and stability were analyzed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of diosgenin,physical mixture and diosgenin albumin nanoparticles(30 mg/kg),respectively,after which blood collection was made at 0.5,1,2,3,4,6,9,12,18 h,HPLC was adopted in the plasma concentration determination of diosgenin,and main pharmacokinetic parameters were calculated.RESULTS The optimial formulation was determined to be 60 mg for diosgenin consumption,8.5 for aqueous phase pH value,0.9 g for albumin consumption,135 MPa for homogenization pressure,and 10 times for homogenization frequency,the encapsulation efficiency,drug loading,Zeta potential and particle size were 93.59%,5.70%,163.72 nm and-21.67 mV,respectively.The albumin nanoparticles demonstrated higher solubility than raw medicine and physical mixture,and higher accumulative dissolution rates within 24 h in simulated gastric juice and simulated intestinal juice than raw medicine.Diosgenin existed in the albumin nanoparticles in an amorphous state,along with good stability within 6 months.Compared with raw medicine and physical mixture,the nanostructured lipid carriers displayed shortened t max(P<0.05),prolonged t 1/2(P<0.05),and increased C max,AUC 0-t,AUC 0-∞(P<0.01),whose relative bioavailability was enhanced to 3.77 times in comparison with raw medicine.CONCLUSION Albumin nanoparticles can enhance the solubility of diosgenin and promote its in vitro drug release,in vivo oral absorption.

关 键 词：薯蓣皂苷元 白蛋白纳米粒 制备 体内药动学 高压均质法 单因素试验 HPLC 

分 类 号：R944[医药卫生—药剂学]