一种基于5-氨基酮戊酸己酯立方液晶的光动力治疗纳米凝胶的制备  

Preparation of a Photodynamic Therapy Nanogel Based on Hexaminolevulinate Cubosomes

作　　者：曾令军 卿洪都 柯月娇 周欣 ZENG Lingjun;QING Hongdu;KE Yuejiao;ZHOU Xin?(Hospital of the Joint Logistics Team,Fuzhou 350025)

机构地区：[1]联勤保障部队第九OO医院药剂科,福建福州350025

出　　处：《中国医药工业杂志》2024年第6期820-828,共9页Chinese Journal of Pharmaceuticals

基　　金：福建省自然科学基金项目(2022J011092、2021J011268)。

摘　　要：该研究以5-氨基酮戊酸己酯(1)为模型药物,采用超声法制备用于光动力治疗的立方液晶(1-Cubs)纳米制剂。以粒径、PDI为评价指标,优化了超声功率、超声时间、单油酸甘油酯(GMO)与泊洛沙姆407(F127)的质量比、载体(GMO与F127总和)与药物的质量比、药物浓度。考察了优化所得的1-Cubs在635 nm激光辐照下对人表皮癌细胞(A431细胞)存活率和ROS含量的影响。然后,以SD大鼠为模型,累积渗透量和皮肤滞留量为评价指标,考察制品的皮肤渗透行为。结果表明,在超声功率400 W、超声时间15 min、GMO与F127质量比4∶1、载体与药物质量比5∶1、药物浓度1%时,所得的1-Cubs能在细胞水平上显著提高1的PDT疗效和ROS产量。基于HPMC制得的1-Cubs(粒径小于200 nm)纳米凝胶对SD大鼠也具有较优的皮肤渗透性,有望成为一种优良的光动力治疗外用制剂。With hexaminolevulinate(1)as a model drug,the nano cubosomes of 1(1-Cubs)for photodynamic therapy(PDT)were prepared by ultrasonication in this study.With particle size and PDI as evaluation indexes,ultrasonic power,ultrasonic time,mass ratio of glycerol monooleate(GMO)to poloxamer 407(F127),mass ratio of carrier(the total amount of GMO and F127)to drug,and drug concentration were optimized.The effect of the optimal 1-Cubs on the survival rate and ROS content of human epidermal cancer cells(A431 cells)under 635 nm laser irradiation was investigated.Then,the skin permeation behaviors of the products were investigated with SD rats as models,and the cumulative transdermal penetration amount and skin retention amount as evaluation indicators.The results showed that the 1-Cubs prepared at ultrasonic power of 400 W,for 15 min,in a 4:1 mass ratio of GMO to F127,in a 5:1 mass ratio of carrier to drug,and drug concentration of 1%had a significant PDT eficacy and ROS production at the cellular level.The 1-Cubs(with the particle size of less than 200 nm)based nanogel with HPMC as the gel matrix also had better skin permeability to SD rats,which was expected to become an excellent topical preparation for PDT.

关 键 词：5-氨基酮戊酸己酯 立方液晶 光动力治疗 经皮渗透 纳米凝胶 

分 类 号：R730.57[医药卫生—肿瘤] R944.9[医药卫生—临床医学]