摘要
目的探索制备蜚蠊提取物长效脂质体的最佳工艺,并评价其对溃疡性结肠炎(UC)模型小鼠的治疗效果。方法采用薄膜分散法制备蜚蠊提取物长效脂质体(CE-Lip),正交实验优化CE-Lip的处方及冻干工艺,进行形态学表征并评价其体外释放速率,并通过UC小鼠模型进行药效学评价。结果最佳制备工艺为胆固醇-磷脂质量比1∶5,提取物-磷脂质量比1∶4,水化时间0.75 h,水化体积3 mL,水化温度30℃;最佳冻干工艺为采用5%甘露醇、10%海藻糖作为混合冻干保护剂;所制得的CE-Lip平均粒径为(276.7±5.6)nm,呈囊泡状结构,冻干后稳定性良好,在体外释放速率显著低于原料药。药效学结果显示CE-Lip可以显著降低UC小鼠的DAI评分、结肠长度、CMDI评分、TNF-α表达量、HS评分,显著升高EGF表达量、杯状细胞中的黏液素表达量。结论获得简便、稳定、重现性良好的CE-Lip制备工艺。制得的CE-Lip,大小分散均匀,稳定性好,具有缓释的效果,相比于普通制剂,CE-Lip显著提高了CE对UC小鼠的治疗作用,为CE-Lip的进一步开发研究奠定了基础。
OBJECTIVE This study aimed to explore the optimal process for preparing long-acting liposomes loaded with cockroach extract(CE-Lip)and to evaluate their therapeutic efficacy against ulcerative colitis(UC).METHODS The CE-Lip was prepared using a thin film dispersion method.Orthogonal experiments were conducted to optimize the formulation and freeze-drying process of CE-Lip.Morphological characterization and in vitro release rate assessment were performed.The therapeutic efficacy of CE-Lip was evaluated using a mouse model of UC.RESULTS The optimal preparation process involved a cholesterol-phospholipid mass ratio of 1∶5,an extract-phospholipid mass ratio of 1∶4,hydration time of 0.75 h,hydration volume of 3 mL,and hydration temperature of 30℃.The optimal freeze-drying process utilized a mixture of 5%mannitol and 10%trehalose as protective agents.The resulting CE-Lip exhibited an average particle size of(276.7±5.6)nm,with a vesicular structure.The stability of CE-Lip after freeze-drying was excellent,and its in vitro release rate was significantly lower than that of the raw material.Pharmacological results demonstrated that CE-Lip significantly reduced DAI scores,colon length,CMDI scores,TNF-αexpression,and HS scores in UC mice,while increasing EGF expression and mucin expression in goblet cells.CONCLUSION A simple,stable,and reproducible process for preparing CE-Lip is established.The resulting CE-Lip exhibits uniform size distribution,good stability,and sustained release effects.Compared to conventional formulations,CE-Lip significantly enhanced the therapeutic effect of CE against UC in mice.This study provides a foundation for further development and research of CE-Lip.
作者
吕廷梅
刘衡
王希通
王宇彤
陈志鹏
LYU Ting-mei;LIU Heng;WANG Xi-tong;WANG Yu-tong;CHEN Zhi-peng(Jiangsu Key Laboratory of Chinese Medicine Processing,Nanjing University of Chinese Medicine,Nanjing 210023,China;Yunnan Provincial Key Laboratory of Insect Biomedicine Research and Development,Dali University,Yunnan Provincial Engineering Research Center for the Development and Comprehensive Utilization of Medicinal Insect Resources,Dali 671000,China)
出处
《南京中医药大学学报》
CAS
CSCD
北大核心
2023年第12期1211-1223,共13页
Journal of Nanjing University of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(81860742,82060780,81773662)
云南省应用基础研究计划项目(202001AT070021)
云南省重大科技专项计划(202002AA100007)。
关键词
蜚蠊提取物
脂质体
正交实验
溃疡性结肠炎
cockroach extract
liposomes
orthogonal experiment
ulcerative colitis