^125Ⅰ-脱氧尿嘧啶核苷-壳聚糖载药纳米微粒的研制和鉴定  

Preparation and in vitro evaluation of chitosan nanoparticles containing 5-[^125Ⅰ] Iodo-2＇deoxyuridine

作　　者：杨辰[2] 刘芬菊[2] 宋妙丽[1] 仲汉彬[1] 石燕[1] 

机构地区：[1]南京医科大学附属苏州医院 [2]江苏省放射医学与防护重点实验室,苏州大学医学部放射医学与公共卫生学院,215123

出　　处：《中华放射医学与防护杂志》2010年第6期650-653,700,共5页Chinese Journal of Radiological Medicine and Protection

基　　金：国家自然科学基金（30870585）;江苏省卫生厅科技项目（Z200622）

摘　　要：目的 研制直径100～200 nm的125Ⅰ-脱氧尿嘧啶核苷-壳聚糖载药纳米微粒（125Ⅰ-UdRCS-DLN）,并进一步分析其药物缓释性能和肿瘤靶向性.方法 采用离子交联法制备CS纳米微粒,以单因素分析和正交试验优化制备条件和工艺;用动态透析法分析其释放特性;激光共聚焦显微镜观察其肿瘤靶向性.结果 按照CS浓度1 g/L,搅拌速度600 r/min,TPP浓度2 g/L,相对分子质量为3×103的条件下得到平均粒径（70.39±5.12）nm的纳米微粒（PDI为0.16±0.012）.透射电镜观察其外观为规整的球形,大小均匀,分散度较好.在投药量为2.96 MBq/ml、pH值为5的条件下,125Ⅰ-UdR-CS-DLN的载药量1253.55 MBq/g,包封率42.35%,具有明显的缓释作用.激光共聚焦显微镜观察结果证明肿瘤细胞在2 h内摄入的纳米粒子明显多于正常细胞.结论 成功制备了直径为（127.81±15.25）nm（PDI为0.240 ±0.035）的125Ⅰ-UdR-CS-DLN,确定了最佳工艺条件.所制备的纳米粒子具有典型的长效缓释制剂特性,并具有肿瘤细胞被动靶向性,为125Ⅰ-UdR应用于肿瘤内照射治疗提供了更有效的途径.Objective To prepare the chitosan nanoparticles loading 5-[125Ⅰ] Iodo-2＇-deoxyuridine （125Ⅰ-UdR-CS-DLN） at 100-200 nm in diameter, and analyze the characteristic of drug sustained-releasing and tumor targeting. Methods Orthogonal experimental design and One-way analysis were applied to optimize the preparation of 125Ⅰ-UdR-CS-DLN using tripolyphosphate cross-linking. Dynamic dialysis was utilized to investigate the in vitro releasing characteristics of the nanoparticles. The tumor targeting effect of the nanoparticles was observed with laser confocal microscopy. Results The optimal conditions for preparing the nanoparticles at particle diameters （70. 39 ± 5.12 ） nm （PDI 0. 16 ± 0. 012 ） were 1 g/L of CS, 2 g/L of TPP, stirring rate 600 r/min, relative molecular mass of CS 3 × 103. The TEM results showed that the exterior of the nanoparticles was spheroid, with a uniform and fine dispersivity. The optimized condition with the initial 125Ⅰ-UdR concentration of 2. 96 MBq/ml at pH5 provided the highest loading capacity （1253. 55 MBq/g） and the highest entrapment rate （42. 35% ）. The in vitro releasing curves of 125Ⅰ-UdR-CS-DLN followed Higuchi equation, shown a characteristic of long-acting preparation.Laser confocal microscopy observations approved that the tumor cells uptake of FITC-CS-nanoparticles were significantly more than that of normal cells. Conclusions Chitosan nanoparticles loading 125Ⅰ-UdR at diameters range 127. 81 ± 15. 25 nm （PDI 0. 240 ± 0. 035 ） were successfully prepared with the optimized conditions, and showed a characteristic of sustained-releasing and tumor targeting. The chitosan-based nanotechnology provided a new and efficient approach for the application of 125Ⅰ-UdR in intracellular radiotherapy for tumor.

关 键 词：^125Ⅰ-UdR 纳米微粒 内照射治疗 

分 类 号：R94[医药卫生—药剂学]