摘要
目的:制备褪黑素固体脂质纳米粒(MT-SLNs),并考察其在小鼠离体皮肤中的透皮吸收特征。方法:以褪黑素(MT)为模型药物,以山嵛酸甘油酯作为油相、泊洛沙姆188(F188)为乳化剂,通过熔融乳化法制备MT-SLNs。使用透射电镜观察MT-SLNs的形态,使用激光粒径分析仪检测其粒径分布,使用红外光谱仪检测其红外光谱特征;采用高效液相色谱法和超滤离心法测定其包封率和载药量,采用Franz扩散池法比较MT-SLNs和MT原料药的体外透皮吸收特征。结果:MT-SLNs的处方中含2.5mg/mLMT原料药、25mg/mL山嵛酸甘油酯和1%F188;所得MT-SLNs呈圆球状,且未见聚集现象发生;其平均粒径为(67.88±0.17)nm,多分散指数为0.188±0.001;其红外光谱图未见N H伸缩和弯曲振动的特征吸收峰,且苯环C H伸缩振动的特征吸收峰红移至1750cm^-1。所得MT-SLNs的包封率为(87.54±5.31)%,载药量为(8.42±0.78)%。MT-SLNs及其原料药的透皮吸收行为均符合零级动力学释放规律;其中,MT-SLNs的稳态透过速率([ 31.71±2.78)μg(/ h· cm^2 )]显著高于其原料药([ 10.32±3.24)μg(/ h· cm^2 )],其滞后时间([ 0.17±0.01)h]显著短于其原料药([ 1.57±0.37)h](P<0.01)。结论:所制MT-SLNs的粒径小,且分布均匀,可促进药物的体外透皮吸收。
OBJECTIVE:To prepare Melatonin solid lipid nanoparticles(MT-SLNs),and to investigate in vitro transcutaneous absorption characteristics of them in isolated skin of mice. METHODS:Using melatonin(MT)as model drug,glycerin sorbate as oil phase,poloxamer 188(F188)as emulsifier,MT-SLNs was prepared by melt-emulsion method. The morphology of MT-SLNs was observed by TEM;the particle size distribution of MT-SLNs was measured by laser particle size analyzer,and the infrared spectrum characteristics were measured by infrared spectroscopy. The entrapped efficiency and drug loading amount were determined by HPLC and ultrafiltration centrifugation method. The transcutaneous absorption characteristics in vitro of MT-SLNs and MT raw material were compared using Franz diffusion cells method. RESULTS:The formulation of MT-SLNs included 2.5 mg/mL MT raw material,25 mg/mL glycerin sorbate and 1%F188. The obtained MT-SLNs were spherical,and no aggregation was observed. Average particle size was(67.88±0.17)nm,and polydispersity index was 0.188±0.001. The characteristic absorption peaks of N-H stretching and bending vibration were not found in infrared spectra,and the characteristic absorption peaks of C-H stretching vibration of benzene ring shifted red to 1 750 cm^-1. The entrapped efficiency and drug loading amount of MT-SLNs were (87.54±5.31)% and(8.42±0.78)%. The transcutaneous absorption behavior of MT-SLNs and MT raw material conformed to 2 zero-order kinetics release rule. The steady-state transmission rate of MT-SLNs ([ 31.71+2.78)μg(/ h· cm^2 )] was significantly higher 2 than that of its raw material ([ 10.32±3.24)μg(/ h· cm^2 )],and its lag time ([ 0.17±0.01)h] was significantly shorter than that of its raw material ([ 1.57±0.37)h](P<0.01). CONCLUSIONS:Prepared MT-SLNs have small particle size and distributed evenly, and can promote in vitro transcutaneous absorption.
作者
王锡辉
王亚平
王向宇
宋宜蕾
王兴荣
王建泽
郝吉福
WANG Xihui;WANG Yaping;WANG Xiangyu;SONG Yilei;WANG Xingrong;WANG Jianze;HAO Jifu(College of Pharmacy,Shandong First Medical University/Shandong Academy of Medical Sciences,Shandong Tai’an 271016,China)
出处
《中国药房》
CAS
北大核心
2019年第14期1936-1940,共5页
China Pharmacy
基金
山东省自然科学基金资助项目(No.ZR2016HM21)
山东省中医药科技发展计划项目(No.2017-240)
山东省抗体制药协同创新中心开放课题(No.CIC-AD1813)
关键词
褪黑素
固体脂质纳米粒
制备
透皮吸收
体外
Melatonin
Solid lipid nanoparticles
Preparation
Transcutaneous absorption
in vitro
