Page 61 - 《中国药房》2022年20期

共载姜黄素/小檗碱自微乳给药系统的制备及评价 Δ

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韩 华 ，梁绿圆 ，季 珂 ，魏炳琦 ，任翎嘉 ，苏洁欣 ，关延彬 （1.河南中医药大学药学院，郑州 450040；
2.河南中医药大学儿科医学院，郑州 450040；3.河南中医药大学仲景学院，郑州 450040）
中图分类号 R943；R965 文献标志码 A 文章编号 1001-0408（2022）20-2487-06
DOI 10.6039/j.issn.1001-0408.2022.20.11
摘 要 目的 制备共载姜黄素/小檗碱的自微乳给药系统（CUR/BER-SMEDDS），并对其理化性质和体外抗肿瘤作用进行评价。
方法 以CUR、BER为模型药物，在筛选油相种类，乳化剂、助乳化剂及二者质量比优化范围的基础上，以粒径和载药量为评价指
标，以油相的质量百分比、乳化剂与助乳化剂的质量比为因素，采用星点设计-效应面法优化其处方并验证；对优化所得CUR/BER-
SMEDDS 的理化性质、体外溶出度、体外抗肿瘤作用进行评价。结果 CUR/BER-SMEDDS 最优处方的油相为中链甘油三酯
（30.97%），乳化剂为聚氧乙烯 40 氢化蓖麻油（46.77%），助乳化剂为聚乙二醇 400（22.26%），乳化剂与助乳化剂质量比为 2.10∶1。
验证实验表明，CUR/BER-SMEDDS的平均粒径为（58.90±5.41）nm，平均载药量为（94.94±3.87）mg/g，与预测值的相对偏差分别
为－2.90%、－0.14%。按最优处方所制CUR/BER-SMEDDS加水乳化后为淡黄色澄清透明液体，其微粒呈圆球形。体外溶出实验
结果显示，制成SMEDDS后，CUR在人工肠液、人工胃液，BER在人工肠液中的累积溶出度均明显高于对应原料药。体外抗肿瘤
实验结果显示，CUR/BER-SMEDDS 对 PC-3、DU-145 细胞的 IC50分别为（17.38±2.84）、（20.89±1.26）μmol/L，均显著低于 CUR、
EBR 单药（P＜0.05）。结论 优化所得 CUR/BER-SMEDDS 制备工艺稳定、可行；所制 CUR/BER-SMEDDS 改善了药物的溶出速
度，且具有更强的体外抗前列腺癌作用。
关键词 姜黄素；小檗碱；自微乳给药系统；处方优化；星点设计-效应面法；抗前列腺癌作用

Preparation and evaluation of curcumin/berberine co-loaded self-microemulsion drug delivery system
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HAN Hua ，LIANG Lüyuan ，JI Ke ，WEI Bingqi ，REN Lingjia ，SU Jiexin ，GUAN Yanbin （1. School of
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Pharmacy，Henan University of Chinese Medicine，Zhengzhou 450040，China；2. School of Pediatrics，Henan
University of Chinese Medicine，Zhengzhou 450040，China；3. School of Zhongjing，Henan University of
Chinese Medicine，Zhengzhou 450040，China）
ABSTRACT OBJECTIVE To prepare curcumin/berberine co-loaded self-microemulsion drug delivery system（CUR/BER-
SMEDDS）and evaluate its physicochemical properties and in vitro anti-tumor effects. METHODS Using CUR and BER as model
drug，based on the screening of the type of oil phase，emulsifier，co emulsifier and their mass ratio，the formulation of CUR/BER-
SMEDDS were optimized by central composite design-response surface methodology，taking particle size and drug loading as
evaluation parameters，with the mass percentage of oil phase and the mass ratio of emulsifier to co emulsifier as factors，and
verification test was conducted. CUR/BER-SMEDDS prepared by optimized formulation were evaluated in terms of physicochemical
properties，in vitro dissolution and in vitro anti-tumor effects. RESULTS The optimized formulation of CUR/BER-SMEDDS
included that the oil phase was medium chain triglyceride （30.97%），the emulsifier was polyoxyl 40 hydrogenated castor oil
（46.77%），the co emulsifier was polyethylene glycol 400（22.26%），and the mass ratio of emulsifier to co emulsifier was 2.10∶1. The
validation experiments showed that mean particle size of CUR/BER-SMEDDS was（58.90±5.41）nm，the average drug loading
was（94.94±3.87）mg/g，and the relative deviations from the predicted values were －2.90% and －0.14%，respectively. The CUR/
BER-SMEDDS prepared by optimal formulation was light yellow，clear and transparent liquid after emulsified with water，and its
particles were spherical. The results of dissolution test in vitro showed that after SMEDDS was made，the cumulative dissolution of
CUR in artificial intestinal fluid and artificial gastric fluid and that of BER in artificial intestinal fluid were significantly higher than
those of its raw material. Results of in vitro anti-tumor experiment showed that IC50 values of CUR/BER-SMEDDS for PC-3 cells
and DU-145 cells were（17.38±2.84）and（20.89±1.26）μmol/L，which were all lower than those of CUR and EBR significantly
（P＜0.05）.CONCLUSIONS The optimized preparation process of CUR/BER-SMEDDS is stable and feasible. The drug release of
CUR/BER-SMEDDS is more complete than that of single
Δ 基金项目 河南省中医药科学研究专项课题（No.20-21ZY2150）；
drug，and has stronger anti-prostate cancer effect in vitro.
河南省高校国家级大学生创新创业训练计划项目（No.202110471009） KEYWORDS curcumin；berberine；self-microemulsion drug
＊第一作者 硕士研究生。研究方向 ：药物新剂型。E-mail：
delivery system；preparation optimization；central composite
2530572936@qq.com。
design-response surface methodology；anti-prostate cancer effect
# 通信作者 教授，硕士生导师，博士。研究方向：中药新剂型与新
技术。电话：0371-65676656。E-mail：guanyanbin96@126.com

中国药房 2022年第33卷第20期 China Pharmacy 2022 Vol. 33 No. 20 ·2487·