摘要
目的构建寡聚透明质酸(5 KDa)修饰的鞣花酸脂质体(EA-HA-L)以提高鞣花酸的水溶性、体外透皮效果和美白活性。方法采用酯化反应制备寡聚透明质酸修饰的胆固醇(HA-Chol),通过FTIR和1H NMR进行结构表征;采用薄膜分散-超声法制备寡聚透明质酸修饰的鞣花酸脂质体,通过Box-Behnken设计-响应面法优化处方工艺,测定最优处方工艺下脂质体的粒径、多分散指数(PDI)、Zeta电位及包封率;比较EA-HA-L和游离EA溶解度的差异;采用大鼠腹部皮肤考察其离体透皮效果;采用多巴氧化法评价其对酪氨酸酶及小鼠黑色素瘤细胞(B16-F10)内酪氨酸酶的抑制作用。结果合成并表征了HAChol;优化后的处方工艺为磷脂与HA-Chol的质量比为10∶1、脂药比为40∶1、水化温度为30℃、水化时间为60 min、超声强度为35%、超声时间为20 min,在最优处方工艺下制得的EA-HA-L粒径为(140.30±1.30)nm,PDI为(0.29±0.01),包封率为91.16%±3.06%,Zeta电位为(-5.67±0.09)mV;EA被脂质体包覆后,在水中的溶解度提高了约40多倍;EA-HA-L在24 h内的累积透皮量为46.98±2.17μg·cm^(-2),24 h后皮肤内滞留量为66.15±0.61μg·cm^(-2),是游离EA的1.72倍(P<0.0001),普通脂质体(EA-L)的1.23倍(P<0.01);在50-400μg·mL^(-1)浓度范围内,EA-HA-L抑制酪氨酸酶的活性均高于游离EA和EA-L。结论利用寡聚透明质酸修饰的胆固醇和大豆磷脂成功制备了粒径小、包封率高的鞣花酸脂质体,该脂质体显著提高了鞣花酸的水溶性,并具有比游离EA和EA-L更好的透皮效果和更强的美白活性。
Objective To construct oligomeric hyaluronic acid(5 KDa)-modified ellagic acid-loaded liposomes(EAHA-L)to improve the aqueous solubility,in vitro transdermal effect and whitening activity of ellagic acid.Methods Oligomeric hyaluronic acid-modified cholesterol(HA-Chol)was prepared by esterification reaction and structurally characterized by FTIR and 1H NMR;Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes were prepared by film dispersion-ultrasound method,and the prescribing process was optimized by Box-Behnken design-response surface method,and the particle sizes,the polydispersity index(PDI),zeta potential and encapsulation rate of liposomes under the optimal prescribing process were determined;the difference in solubility between EA-HA-L and free EA was evaluated;in vitro transdermal effect of liposomes were investigated using rat abdominal skin;inhibitory effect on tyrosinase and intracellular tyrosinase in mouse melanoma cells(B16-F10)was surveyed via dopa oxidation method.Results HA-Chol was synthesized and characterized;the optimized prescription process was mass ratio of 10∶1 for soy phospholipids to HA-Chol,lipid-drug ratio of 40∶1,hydration temperature of 30℃,hydration time of 60 min,ultrasound intensity of 35%,ultrasound time of 21 min,and the particle size of EA-HA-L produced under the optimized prescription process was(140.30±1.30)nm,PDI was(0.29±0.01),the encapsulation rate of ellagic acid was 91.16%±3.06%,and the zeta potential was(-5.67±0.09)mV;after EA was encapsulated by liposomes,the solubility of EA in water increased by about 40-fold;the cumulative transdermal amount of EA-HA-L was 46.98±2.17μg·cm^(-2) in 24 h,and the intradermal retention was 66.15±0.61μg·cm^(-2),which was 1.72 times higher than that of free EA(P<0.0001)and 1.23 times higher than plain liposome(EA-L)(P<0.01);and the tyrosinase inhibitory activity of EA-HA-L was higher than that of both free EA and EA-L in the EA concentration range of 50-400μg·mL-1.Conclusion Oligomeric hyaluronic acid-modifi
作者
杨晓婧
陈赤清
苗开元
胡俊杰
郑国华
陈欣妍
石召华
Yang Xiaojing;Chen Chiqing;Miao Kaiyuan;Hu Junjie;Zheng Guohua;Chen Xinyan;Shi Zhaohua(School of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065,China;Wufeng Chicheng Biotechnology Limited Company,Yichang 443400,China;Hubei University of Traditional Chinese Medicine,Key Laboratory of Resources and Compound of Traditional Chinese Medicine,Ministry of Education,Wuhan 430065,China;Hubei Shizhen Laboratory,Wuhan 430065,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第12期3856-3865,共10页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
校级中医药重点专项(2022ZZXZ003):中医药化妆品研发关键技术体系构建,负责人:石召华
校级中医药重点专项(2023ZZXJB002):基于五峰特色中药材五倍子系列功效护肤品的开发及产业化,负责人:石召华。
关键词
鞣花酸
寡聚透明质酸
脂质体
离体透皮
美白
Ellagic acid
Oligomeric hyaluronic acid
Liposomes
Transdermal effect
Whitening activity
