黄体酮脂质体微针的制备及体外性质考察  

Preparation and in vitro characterization of progesterone liposome microneedles

作　　者：贺宏吉 沈琪[1,2,3] 王昭志[1] 卡迪热娅·艾克拉木 白静雅 王梅 HE Hongji;SHEN Qi;WANG Zhaozhi;Kadireya Aikelamu;BAI Jingya;WANG Mei(College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China;Engineering Research Center of Xinjiang and Central Asian Medicine Resources,Ministry of Education,Urumqi 830017,China;Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology,Urumqi 830017,China)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830017 [2]新疆及中亚特色医药资源教育部工程研究中心,乌鲁木齐830017 [3]新疆天然药物活性组分与释药技术重点实验室,乌鲁木齐830017

出　　处：《新疆医科大学学报》2023年第10期1369-1375,共7页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金项目(2021D01C287);新疆维吾尔自治区重大科技专项项目(2022A03007-4)。

摘　　要：目的制备黄体酮脂质体,优选黄体酮脂质体微针的处方工艺,考察黄体酮脂质体微针的体外释放及经皮渗透效果。方法制备黄体酮脂质体,以包封率、粒径及电镜下形态进行表征。将黄体酮脂质体与微针基质材料甲基丙烯酰化明胶(GelMA)混合,采用溶剂铸造法制备微针阵列,对微针的皮肤穿刺性、载药量、体外释放、经皮渗透性能进行考察。结果制得的黄体酮脂质体包封率为(70.88±2.07)%,粒径为(266.93±9.05)nm,聚合物分散性指数(PDI)为(0.23±0.03),72 h体外释放率为(83.58±2.54)%。黄体酮脂质体微针最优工艺为:以15%的甲基丙烯酰化明胶为微针基质,光引发剂LAP浓度为0.25%,制得微针的载药量为(329.83±3.00)μg/cm^(2),光固化后,微针溶胀度均在200%以上。在体外释放实验中,分别经光固化1、2、3 min的黄体酮脂质体微针释放量随光固化时间的延长而下降。在体外经皮渗透实验中,在96 h时光固化1 min的累计渗透量为(167.08±4.75)μg/cm^(2),光固化2 min的累计渗透量为(159.69±6.04)μg/cm^(2),3 min的累计渗透量为(135.47±11.34)μg/cm^(2)。结论优选出的黄体酮脂质体微针成型性好,机械强度高。相较于脂质体,黄体酮微针能够更加有效地经皮渗透,可改善黄体酮透皮制剂的透皮性能。Objective To prepare progesterone liposomes,to optimize the prescription process of progesterone liposome microneedles and to investigate the in vitro release and transdermal penetration of progesterone liposome microneedles.Methods Progesterone liposomes were prepared and characterized by encapsulation rate,particle size and morphology under electron microscopy.The progesterone liposomes were later mixed with the microneedle matrix material methacrylate-based gelatin(GelMA)to prepare microneedle arrays with using the solvent casting method to investigate the skin penetration,drug loading,in vitro release and transdermal penetration properties of the microneedles.Results The progesterone liposome encapsulation rate was(70.88±2.07)%;the particle size was(266.93±9.05)nm,the polymer dispersity index(PDI)was(0.23±0.03);the 72 h in vitro release rate was(83.58±2.54)%.The optimal technology of progesterone liposome microneedle was as follows:15%GelMA was used as microneedle matrix,the concentration of photoinitiator LAP was 0.25%,the drug loading capacity of microneedles was(329.83±3.00)μg/cm^(2),and the expansion degree of microneedles was above 200%after photocurig.In vitro release experiment,the amount of progesterone lipid microneedles released by light curing for 1,2 and 3 min respectively decreased with the extension of light curing time.In vitro percutaneous permeation experiments,the cumulative amount of progesterone liposome microneedles released after 1 min of light curing at 96 h was(167.08±4.75)μg/cm^(2),(159.69±6.04)μg/cm^(2) for 2 min and(135.47±11.34)μg/cm^(2) for 3 min of light curing.Conclusion The preferred progesterone liposome microneedles had good formability and high mechanical strength.Compared with liposomes,progesterone microneedles can penetrate more effectively transdermally and can improve the transdermal performance of progesterone transdermal formulations.

关 键 词：黄体酮 脂质体 微针 透皮给药系统 光固化材料 

分 类 号：R943[医药卫生—药剂学]