甲氨蝶呤与葫芦素B共载纳米脂质载体的制备及其体外评价  

Preparation and in vitro evaluation of co-loaded nanostructured lipid carriers for methotrexate and cucurbitacin B

作　　者：李昊 鲍婷琦 黄馨怡 周建文 苗雯凯 吴丽红[2] 王子珣 曹立新[2] 韩翠艳[1] LI Hao;BAO Ting-qi;HUANG Xin-yi;ZHOU Jian-wen;MIAO Wen-kai;WU Li-hong;WANG Zi-xun;CAO Li-xin;HAN Cui-yan(School of pharmacy,Qiqihar Medical University,Qiqihar 161006,China;The First Affiliated Hospital of Qiqihar Medical University,Qiqihar 161042,China)

机构地区：[1]齐齐哈尔医学院药学院,齐齐哈尔161006 [2]齐齐哈尔医学院第一附属医院,齐齐哈尔161042

出　　处：《中国新药杂志》2025年第7期761-770,共10页Chinese Journal of New Drugs

基　　金：2021年齐齐哈尔医学科学院临床科研基金资助项目(QMSI2020L-01)。

摘　　要：目的:本研究以纳米结构脂质载体(nanostructured lipid carrier,NLC)同时装载甲氨蝶呤(methotrexate,MTX)与葫芦素B(cucurbitacinB,CuB)(MTX-CuB-NLC),对其进行处方优化及体外评价。方法:建立MTX和CuB体外高效液相色谱分析方法。采用熔融乳化-低温固化法制备MTX-CuB-NLC。以包封率及载药量为评价指标进行单因素考察,用Box-Behnken设计-响应面法筛选出最优处方。通过纳米粒度测定仪对制剂的粒径、多分散性指数(polydispersity index,PDI)、Zeta电位进行考察。通过透射电子显微镜考察制剂的外观形态。并通过粒径、Zeta电位的变化对其储存稳定性进行考察。采用透析袋法测定该给药系统的体外释药情况。结果:MTX-CuB-NLC最优处方为MTX 0.7 mg,CuB 0.5 mg,混合脂肪酸甘油酯104 mg,ELP 96 mg,水相体积4 mL,聚乙烯醇(polyvinyl alcohol,PVA)44 mg,其中包封率MTX(61.03±2.40)%、CuB(81.02±1.61)%、载药量MTX(0.25±0.02)%、CuB(0.23±0.02)%,平均粒径为(44.13±1.40)nm,PDI为(0.279±0.12),Zeta电位为-(17.10±4.98)mV。透射电镜下为类圆形,表面光滑,分散性良好。其在14 d的储存过程中表现出良好的稳定性。48 h累计释放量为MTX(86.01±2.25)%、CuB(73.72±1.97)%。结论:本实验成功制备了MTX-CuB-NLC,制剂稳定、药物缓释,为该制剂的进一步研究奠定了基础。Objective:In this study,a nanostructured lipid carrier(NLC) was loaded with methotrexate(MTX) and cucurbitacin B(CuB),resulting in the formulation MTX-CuB-NLC,which was optimized and evaluated in vitro.Methods:An in vitro high-performance liquid chromatography analysis method of MTX and CuB was established.The MTX-CuB-NLCs were prepared using a melt emulsification low-temperature curing method.A single-factor analysis was conducted by using encapsulation efficiency and drug loading as evaluation indicators,to identify the optimal prescription using Box-Behnken design response surface methodology.The particle size,polydispersity index(PDI),and Zeta potential of the formulation were evaluated by means of nanoparticle size analyzer.The appearance and morphology of the formulation were examined through transmission electron microscopy.And its storage stability was investigated by changes in particle size and Zeta potential.The in vitro drug release of the drug delivery system was assessed using the dialysis bag method.Results:The optimal formulation of MTX-CuB-NLC was as follows:MTX 0.7 mg,CuB 0.5 mg,mixed fatty acid glyceride 104 mg,ELP 96 mg,water phase volume 4 mL,and PVA 44 mg.The entrapment efficiencies were MTX(61.03±2.40)%,CuB(81.02±1.61)%.The drug loading capacities were MTX(0.25±0.02)%,CuB(0.23±0.02)%.The average particle size(44.13±1.40) nm,PDI(0.279±0.12),Zeta potential-(17.10±4.98) mV.Under transmission electron microscopy,the particles appeared quasi-circular with smooth surface and excellent dispersion.They showed favorable stability during storage over 14 days.The cumulative release of MTX and CuB in 48 h was(86.01±2.25)% and(73.72±1.97)%,respectively.Conclusion:In this study,MTX-CuB-NLC was successfully prepared.The preparation method was stable and sustained-release,which laid the foundation for the further study of the preparation.

关 键 词：甲氨蝶呤 葫芦素B 纳米结构脂质载体 

分 类 号：R965[医药卫生—药理学]