颈淋巴结靶向抗癌纳米微粒的研制及其对口腔癌颈淋巴结转移灶靶向治疗的研究  

Preparation of anticancer nanoparticales for targeting cervical lymph nodes and the study of targeting cervical lymph nodes metastatic foci in oral carcinoma by the nanoparticales

作　　者：杨凯 温玉明[1] 

机构地区：[1]四川大学华西口腔医学院口腔颌面外科

出　　处：《现代口腔医学杂志》2006年第4期337-340,共4页Journal of Modern Stomatology

基　　金：卫生部科学研究基金(编号:98-1-221);重庆市科委应用基础研究项目[渝科发计字(2003)43号];重庆市卫生局科研项目(2001年);重庆医科大学科技基金(编号:XB200207)资助项目

摘　　要：目的根据口腔癌周毛细淋巴管的解剖生理特点,制备对口腔癌颈淋巴结转移灶具有靶向性的抗癌蚋米微粒。方法以聚乳酸(PAL)为载体,以对口腔鳞癌细胞有强大杀伤作用的葫芦素BE(CuBE)为模型药物,用乳化一溶荆挥发法制备葫芦素BE聚乳酸蚋米微粒(CuBE-PLA-NP);在体内外对CuBE-PLA-NP相关性质检测的基础上,建立昆明小鼠颊癌颈淋巴结转移模型。以CuBE-PLA-NP为实验组,CuBE为对照组．分别行癌用粘膜下注射,注射后在15个不同时间点处死动物,用高效液相色谱仪检测血、心、肝、脾、肺、肾和颈淋巴结内在不同时间点的药物浓度。以考察药物在体内的组织分布情况,并现察各组对颈淋巴结转移灶的治疗疗效。结果①CuBE-PLA-NP粒径分布范围为47nm-120nm,平均粒径为85nm,载药量为(23．03±O．47％)．包封率为(93．00±0．10％),体外释药规律表明与Higuchi方程拟合,合成的CuBE-PLA-NP没有降低CuBE成份的抗癌活性并适合于行局部注射。②实验组中颈淋巴结转移灶内药物相对百分比远远高于对照组(P<O．05),而血中药物浓度显著低于对照组(P<0．05)。实验组中颈淋巴结转移癌细胞可见有明显坏死,随着时间延长。颈转移灶内坏死区域增大。而对照组中颈淋巴蛄转移癌细胞在各个时间点均未出现坏死。结论平均粒径为85nm的CuBE-PLA-NP对口腔癌颈淋巴结转移灶具有良好的靶向性和确切的治疗疗效,同时降低了药物的全身毒副作用。Objective Anticancer nano- particles for targeting cervical lymph nodes are prepared on the base of the physiologic and anatomic properties of the lymphatic capillaries around caneer. Methods Polylactic acid （PLA） was selected as the carrier material, CucurbitacinBE（CuBE） with very high anticancer activity against oral squamoua cell carcinoma as the model drug, CucurbitacinBE polyhctic acid nano - particles （CuBE- PLA- NP） was prepared by the emulsion solvent evaporation method, and then models mice were established with oral cancer cervical lymph node metastasis , CuBE- PLA- NP（experimential group） and CuBE（ control group）were injected in submucosal of model mice around caneer respectively. The medicine concentration of blood, heart, liver, slpeen, lung, kidney and cervical lymph nodes were measured by high performance liquid chromatography at 15 different time points. Therapeutic effect and medicine distribution in tissue were evaluated. Results ① The diameter distribution for CuBE - PLA - NP was from 47nm-120nm, the average diameter was 85nm, Medicine Loading （ML） and Embedding ration （ER） were （23.03 ± 0.47） 96 and （93.00 ± 0.10） % respectively. The Higuchi equation was adequate to fit the release Curve of CuBE - PLA - NP, anticancer effects of CuBE within CuBE - PLA- NP was not decreased. ②Medicine relative percentage in cervical lymph node of CuBE - PLA - NP group was much higher than that of CuBE group （ P 〈 0.05 ）, the CuBE concentrations in the blood in CuBE - PLA - NP group was much lower than that in CuBE group（ P 〈 0.05）. Metastatic cancer cell in cervical lymph node of CuBE- PLA- NP group showed necrosis after injecting CuBE- PLA- NP. With time prolonging, necrotic area became gradually large. However, necrosis of cancer cell was not found in CuBE group at all time points. Conclusion The average diameter 85nm anticancer nano - particles can specifically deliver anticancer medicine to the cervical lymph node metastaic foci by submucosal injection a

关 键 词：蚋米 口腔癌 颈 淋巴结 转移 靶向治疗 

分 类 号：R739.8[医药卫生—肿瘤]