中华放射医学与防护杂志
中華放射醫學與防護雜誌
중화방사의학여방호잡지
Chinese Journal of Radiological Medicine and Protection
2010年
6期
650-653,700
,共5页
杨辰%刘芬菊%宋妙丽%仲汉彬%石燕
楊辰%劉芬菊%宋妙麗%仲漢彬%石燕
양신%류분국%송묘려%중한빈%석연
125Ⅰ-UdR%纳米微粒%内照射治疗
125Ⅰ-UdR%納米微粒%內照射治療
125Ⅰ-UdR%납미미립%내조사치료
125Ⅰ-UdR%Nanoparticle%Inner radiotherapy
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.
目的 研製直徑100～200 nm的125Ⅰ-脫氧尿嘧啶覈苷-殼聚糖載藥納米微粒(125Ⅰ-UdRCS-DLN),併進一步分析其藥物緩釋性能和腫瘤靶嚮性.方法 採用離子交聯法製備CS納米微粒,以單因素分析和正交試驗優化製備條件和工藝;用動態透析法分析其釋放特性;激光共聚焦顯微鏡觀察其腫瘤靶嚮性.結果 按照CS濃度1 g/L,攪拌速度600 r/min,TPP濃度2 g/L,相對分子質量為3×103的條件下得到平均粒徑(70.39±5.12)nm的納米微粒(PDI為0.16±0.012).透射電鏡觀察其外觀為規整的毬形,大小均勻,分散度較好.在投藥量為2.96 MBq/ml、pH值為5的條件下,125Ⅰ-UdR-CS-DLN的載藥量1253.55 MBq/g,包封率42.35%,具有明顯的緩釋作用.激光共聚焦顯微鏡觀察結果證明腫瘤細胞在2 h內攝入的納米粒子明顯多于正常細胞.結論 成功製備瞭直徑為(127.81±15.25)nm(PDI為0.240 ±0.035)的125Ⅰ-UdR-CS-DLN,確定瞭最佳工藝條件.所製備的納米粒子具有典型的長效緩釋製劑特性,併具有腫瘤細胞被動靶嚮性,為125Ⅰ-UdR應用于腫瘤內照射治療提供瞭更有效的途徑.
목적 연제직경100～200 nm적125Ⅰ-탈양뇨밀정핵감-각취당재약납미미립(125Ⅰ-UdRCS-DLN),병진일보분석기약물완석성능화종류파향성.방법 채용리자교련법제비CS납미미립,이단인소분석화정교시험우화제비조건화공예;용동태투석법분석기석방특성;격광공취초현미경관찰기종류파향성.결과 안조CS농도1 g/L,교반속도600 r/min,TPP농도2 g/L,상대분자질량위3×103적조건하득도평균립경(70.39±5.12)nm적납미미립(PDI위0.16±0.012).투사전경관찰기외관위규정적구형,대소균균,분산도교호.재투약량위2.96 MBq/ml、pH치위5적조건하,125Ⅰ-UdR-CS-DLN적재약량1253.55 MBq/g,포봉솔42.35%,구유명현적완석작용.격광공취초현미경관찰결과증명종류세포재2 h내섭입적납미입자명현다우정상세포.결론 성공제비료직경위(127.81±15.25)nm(PDI위0.240 ±0.035)적125Ⅰ-UdR-CS-DLN,학정료최가공예조건.소제비적납미입자구유전형적장효완석제제특성,병구유종류세포피동파향성,위125Ⅰ-UdR응용우종류내조사치료제공료경유효적도경.
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.
