多肽修饰载紫杉醇PLGA微球的制备技术  

Construction of peptide-conjugated paclitaxel-loaded PLGA microspheres

作　　者：袁晓燕[1] 刘为青[2] 董坚[1] 高嫦娥[2] 刘冬[3] 袁明龙[3] 

机构地区：[1]昆明医科大学第三附属医院.云南省肿瘤医院,云南昆明6500118 [2]昆明医科大学第一附属医院生物治疗中心,云南昆明650032 [3]云南民族大学化学与生物技术实验室,云南昆明650500

出　　处：《西部医学》2015年第11期1626-1630,共5页Medical Journal of West China

基　　金：云南省教育厅科学研究基金重大专项(ZD2013005);云南省细胞治疗转化医学重点实验室资助

摘　　要：目的 以乳酸-羟基乙酸共聚物[poly（lactic-co-glycolic acid）,PLGA]为载体,研究经三阴性乳腺癌特异性多肽修饰的载紫杉醇PLGA微球（PI-PTX/PLGA微球）的构建方法,建立新型的经多肽修饰的载药方式。方法 以乳化-溶剂挥发法制备包载紫杉醇的PLGA微球（PTX/PLGA微球）,采用EDC/NHS体系作为交联剂,将PI多肽连于PTX/PLGA微球表面,通过扫描电镜、激光粒度仪、高效液相色谱仪和倒置荧光显微镜分析微球的表面形态、粒径、载药量、包封率及多肽连接状态。结果 多肽修饰的载药微球呈圆球形,分散性好,形态规整,无聚集现象,球体表面未见明显空隙,激光粒度仪测得空白PLGA微球、PTX/PLGA微球和PI-PTX/PLGA微球的平均粒径分别为14.65μm、15.07μm和17.15μm。高效液相色谱法测得紫杉醇在1.0~50μg/ml浓度范围内,峰面积（Y）对紫杉醇浓度（X）有良好的线性关系,得到标准曲线方程为Y=33.783X＋2.7098（R2=1）,由此计算PTX/PLGA微球和PI-PTX/PLGA微球的载药量和包封率分别为2.8%和91%、2.5%和84%。多肽修饰的载药微球,表面呈绿色荧光,EDC/NHS交联体系对微球结构无明显影响。结论 EDC/NHS交联体系适用于多肽与PLGA微球的连接,稳定性好。同时,也为靶向生物分子与载药微球的结合提供了新的途径。Objective Poly（lactic-co-glycolic acid）（PLGA） and breast cancer peptides were used to construct pep- tide-conjugated paclitaxel-loaded PLGA microspheres,in order to obtain a new method of building peptide-decorated drug- loaded microspheres. Methods Paclitaxel was encapsulated in PLGA microspheres through solvent evaporation. The peptide-PI was cross-linked to their surface by EDC/NHS crosslinking agents. The surface morphology, size, drug load- ing and connection of PTX/PLGA microspheres and PI-PTX/PLGA microspheres were analyzed by SEM,laser particles size analyser, HPLC and inverted fluorescence microscope. Results PI-PTX/PLGA microspheres were spheriodal. It had good dispersion in water. Average size of PTX-free PLGA microspheres, PTX/PLGA microspheres and PI-PTX/PLGA microspheres were 14.6Stem, 15.07vm and 17.15tim. The Peak area （Y）and paclitaxel concentration（X） had good linear relation through HPLC measurement,acquiring the standard curve equation： Y=33. 783X＋ 2. 7098（R2=1）. The drug loading and encapsulation efficiency of PTX/PLGA microspheres and PI-PTX/PLGA microspheres were 2.8 % and 91 %, 2.5 % and 84 %, respectively. PI-PTX/PLGA microspheres were sphericity appearing green fluorescence. EDC/NHS did not damage the surface morphology of particles. Conclusion EDC/NHS crosslinking agents can connect peptides with PLGA microspheres tightly. This study provide a new way for peptide-modified drug-loaded particles.

关 键 词：紫杉醇 乳酸-羟基乙酸共聚物 PI多肽 微球 高效液相色谱法 EDC/NHS交联剂 

分 类 号：R965.2[医药卫生—药理学]