柠檬烯阴离子脂质体的制备及初步药效评价
Preparation and Preliminary Pharmacodynamic Evaluation of Anionic Liposomes Loaded with Limonene
黎娜 1邹娅 2郑晓艳 1董定国 1陈柳葵1
作者信息
- 1. 湛江中心人民医院药学部,广东湛江 524045
- 2. 成都市第二人民医院临床药学科,四川成都 610017
- 折叠
摘要
采用乙醇注入法构建了载柠檬烯的二棕榈酰磷脂酰甘油(DPPG)阴离子长循环脂质体,并以脂质体的粒径和PDI作为评价指标,优化处方.所得优化处方为氢化大豆磷脂、DPPG、N-(羰基-甲氧基聚乙二醇2000)-1,2-二硬脂酰-sn-甘油-3-磷酰乙醇胺钠盐和胆固醇的物质的量比例46.5∶10∶38.5∶5.优化脂质体的粒径为(62.84±2.36)nm,PDI为0.241±0.012;并且,在透射电镜下呈球形,粒度分布相对均一,具有明显的磷脂双分子层结构.载药阴离子脂质体的血清稳定性和血液相容性良好,并能在4℃条件下稳定保存4 d;在PBS中前12 h内的累积释放率约为50％,48 h累积释放率约为80％,呈现出缓慢释放的现象.在小鼠模型中的药效学研究表明,该柠檬烯阴离子脂质体可改善胆固醇沉着症小鼠胆囊体积增大、胆汁混浊和胆石增多的情况,对肝脏和胆囊部位的炎症反应也具有一定的抑制作用.
Abstract
Limonene-loaded dipalmitoyl phosphatidylglycerol(DPPG)anionic long cycle liposomes were constructed by ethanol injection,and the formulation of the liposomes were optimized with particle size and PDI as the evaluation indexes.The results showed that the optimal liposomes were prepared in a 46.5∶10∶38.5∶5 molar ratio of hydrogenated soybean phospholipid,DPPG,N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-sn-glycerol-3-phosphoethanolamine sodium and cholesterol.The particle size and PDI of the optimized liposomes were(62.84±2.36)nm and 0.241±0.012,respectively.Moreover,the products appeared spherical with relatively uniform distribution and obvious phospholipid bilayer structure in the TEM images.The serum stability and blood compatibility of the drug-loaded anionic liposomes were good and could be stably stored at 4 ℃ for 4 d.The cumulative release rate within the first 12 h in PBS was about 50％,and was about 80％at 48 h,showing a slow release characteristics.Pharmacodynamic studies in mouse models showed that the limonene anionic liposomes could improve the enlargement of gallbladder size,bile turbidity and gallstones in cholesterolosis mice,and also inhibit the inflammation in liver and gallbladder sites.
关键词
柠檬烯/阴离子脂质体/缓释/胆囊/保护Key words
limonene/anionic liposome/sustained-release/gallbladder/protection引用本文复制引用
出版年
2024
NETL
NSTL
万方数据