载MD-CPT透明质酸纳米微乳经皮给药作用于瘢痕修复的研究  

The Study of HA Nanoemulsionloading MD-CPT by Transdermal Delivery Effect on Keloid Repair

作　　者：高媛媛[1] 孔明[1] 程晓杰[1] 王志国[2] 陈西广[1] 

机构地区：[1]中国海洋大学海洋生命学院,青岛266003 [2]青岛大学医学院附属医院,青岛266013

出　　处：《生物化学与生物物理进展》2014年第2期202-208,共7页Progress In Biochemistry and Biophysics

基　　金：国家科技部国际合作重点项目(2013DFG32880);国家自然科学基金(31000423);教育部博士点基金(20120132110012)资助项目~~

摘　　要：喜树碱衍生物对瘢痕疙瘩成纤维细胞的增殖有明显的抑制作用，为提高药物利用度，提供透皮给药的治疗途径，本文采用微乳法制备了一种新的O／W型透明质酸纳米载体（HA-GMS），包载药物10，11-亚甲二氧基喜树碱（MD-CPT），制备过程中无酒精，且没有使用化学增强剂，经透射电镜和激光粒度仪分别测得HA-GMS纳米乳粒径为（177.33±27.11）nm，zeta电位为-15.6±1.7，多分散系数为0.55±0.01，纳米微乳对MD-CPT药物的包封率为（77.85±1.29）％，且稳定性良好．用MTT法检测HA-GMS对人正常细胞HSF、HUVECs的作用，细胞相对存活率为75％～95％，生物相容性良好，用HA-GMS对瘢痕疙瘩成纤维细胞培养48h，其生长抑制率为28.2％．HA-GMS纳米乳运载的MD-CPT皮肤渗透量明显高于对照组MD-CPT乙醇溶液对皮肤的渗透量，作用4h的累积渗透量分别为（660.7±20.54）μg／cm^2和（102.73±13.81）μg／cm^2，HA-GMS纳米乳明显增加了MD-CPT的透皮效率，本研究结果为透皮给药治疗瘢痕疾病提供了基础．Camptothecin derivatives have an obvious inhibitory effect on keloid fibroblasts proliferation. In order to improve the utilization rate of drug and provide a transdermal drug treat method, a non-alcoholic hyaluronic acid O/W type nanoemulsion without any chemical enhancers was made to encapsulate 10,11-methylenedioxycamptothecin （MD-CPT）. We used transmission electron microscopy （TEM） and laser particle size instrument to survey the HA-GMS nanoemulsion morphology observation, and measured the particle size of （177.32±27.11） nm, the zetaelectric potential of-15.6±1.7, the PdI of 0.55±0.01 and the encapsulation efficiency of （77.85±1.29）%. Determination by MTT method was used to research the effect of biomaterial HA-GMS on HSF cells and HUVECs cells, and the relative cell viability range from 75%±95%, having good biocompatibility, and for keloid fibroblasts culture, growth inhibition rate was 28.2%.The transdermal effect of HA-GMS nanoemulsion carrying MD-CPT was obviously better than that of the control group （CPT MD-CPT ethanol solution）, treating for 4 h, the cumulative drug permeation was （660.72±20.54） p,g/cm2 and （102.73±13.81） p,g/cm2 respectively, the HA-GMS nanoemulsion significantly increased the efficiency of MD-CPT through skin, which may provide a good drug delivery approach.

关 键 词：透明质酸 纳米微乳 喜树碱衍生物 透皮给药 瘢痕疙瘩 

分 类 号：R944.1[医药卫生—药剂学] Q819[医药卫生—药学]