摘要
目的制备野黄芩素纳米晶体(scutellarein nanocrystals,Scu-NCs),进行药剂学性质研究,并考察其对小鼠皮肤干燥瘙痒模型的治疗效果。方法采用反溶剂沉淀技术制备Scu-NCs,并通过冷冻干燥技术将其固化成固体粉末;测定ScuNCs的平均粒径、分散系数、ζ电位并观察其微观结构;差示扫描量热法(differential scanning calorimetry,DSC)及傅里叶变换红外光谱法(Fourier transform infrared spectroscopy,FTIR)分析其晶型及化学结构的变化;测试其体外药物溶出速率和其凝胶剂的体外释放度;评价野黄芩素及Scu-NCs凝胶剂经皮给药对丙酮/乙醚和水(acetone-ether-water,AEW)诱导的小鼠干皮瘙痒模型的止痒作用。结果制备得到的Scu-NCs平均粒径为(379.1±1.7)nm,多分散系数(polydispersity index,PDI)值为0.238±0.081,ζ电位为(25.50±0.25)mV;野黄芩素纳米化后野黄芩素的晶型和化学结构未发生明显变化;ScuNCs冷冻干燥后粒径无明显变化;野黄芩素纳米化后提高了药物2 h内的溶出速率、溶出度及Scu-NCs凝胶剂6 h内的体外释放度;与AEW模型组相比,野黄芩素、Scu-NCs凝胶剂给药组可明显降低小鼠1 h内抓挠次数,抑制颈背部表皮增厚及皮肤中白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)的表达,且Scu-NCs对AEW模型抑制效果更明显。结论Scu-NCs粒径较小且均匀,其纳米化后晶型和化学结构没有发生明显改变;将野黄芩素制备成纳米晶体后,可明显改善药物的溶出度与体外释放度,对皮肤局部慢性瘙痒具有更好的治疗效果。
Objective To prepare scutellarein nanocrystals(Scu-NCs),investigate their pharmaceutical characteristics and their therapeutic effects on a mouse model of dry and itchy skin.Methods The Scu-NCs were prepared by anti-solvent precipitation technique and solidified into solid powder by freeze-drying technique;The average particle size,dispersion coefficient,ζpotential,and microstructure of Scu-NCs were determined;Differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR)were used to analyze the changes in crystalline shape and chemical structure of Scu-NCs;The dissolution rate of the drug and the release degree of the gel in vitro were tested;and the itch-relieving effects of the transdermal administration of scutellarein and Scu-NCs gel on the mouse model of dry and itchy skin induced by acetone/ethyl ether and water(AEW)were evaluated.Results The average particle size of the prepared Scu-NCs was(379.1±1.7)nm,the polydispersity index(PDI)value was 0.238±0.081,and theζpotential was(25.50±0.25)mV;The crystalline shape and chemical structure of scutellarein after nano conversion did not change significantly;There was no significant change in the particle size of Scu-NCs after freeze-drying;The nano conversion of scutellarein improved the drug dissolution rate within 2 h,dissolution degree and the release degree of the Scu-NCs gel in vitro within 6 h;Compared with the AEW model group,the scutellarein and Scu-NCs gel administration group could significantly reduce the number of scratching within 1 h,inhibit epidermal thickening of the nape of the neck and expression of interleukin-6(IL-6),interleukin-1β(IL1β),and tumor necrosis factor-α(TNF-α)in the skin,and the inhibitory effect of Scu-NCs was more obvious on the AEW model.Conclusion The particle size of Scu-NCs was small and uniform,and there was no significant change in the crystal shape and chemical structure after its nano conversion;The preparation of scutellarein into nanocrystals significantly improved the dissolution and in
作者
刘新颖
王富江
葛海涛
LIU Xinying;WANG Fujiang;GE Haitao(Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Suzhong Pharmaceutical Research Institute Co.,Ltd.,Nanjing 210031,China)
出处
《中草药》
CAS
CSCD
北大核心
2024年第9期2946-2954,共9页
Chinese Traditional and Herbal Drugs
基金
泰州市“凤城英才计划”青年科技人才托举工程
南京中医药大学自然科学基金项目(XZR2020099)。
关键词
野黄芩素
纳米晶体
凝胶
慢性瘙痒
外用制剂
反溶剂沉淀技术
冷冻干燥技术
白细胞介素
肿瘤坏死因子-α
scutellarein
nanocrystals
gel
chronic itching
external preparations
anti-solvent precipitation technique
freeze-drying technique
interleukin
tumor necrosis factor-α
