葫芦素BE聚乳酸纳米微粒对口腔癌颈淋巴结转移灶的靶向性评价

The Study of Cucurbitacin BE Polylactic Acid Nanoparticles Delivering Cucurbitacin BE to Metastasized Cervical Lymph Nodes in Mice with Oral Cancer

目的 探讨平均粒径为 85nm的葫芦素BE聚乳酸纳米微粒 (CuBE_PLA_NP)对口腔癌颈淋巴结转移灶的靶向性及靶向程度。方法 用高颈淋巴结转移癌株U1 4建立昆明小鼠颊癌颈淋巴结转移模型 ,用CuBE_PLA_NP和葫芦素BE(CuBE)分别行癌周黏膜下注射 ,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、肾和颈淋巴结在不同时间点的药物浓度 ,用靶向指数、选择性指数、靶向效率、相对靶向效率和药物峰浓度比来全面评价CuBE_PLA_NP的颈淋巴结靶向性。结果 ①CuBE_PLA_NP组各时间点颈淋巴结内药物浓度远高于CuBE组 ,且药物持续作用时间明显长于CuBE组 ;②CuBE_PLA_NP组药物对颈淋巴结转移灶的 5个靶向指标值均显著高于CuBE组 ;③CuBE_PLA_NP组各时间点血、心、肝、脾、肺、肾中药物浓度显著低于CuBE组。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 ,既提高颈淋巴结转移灶内药物浓度和延长药物持续作用时间 ,同时也降低了血、心、肝、脾、肺、肾中药物浓度。

Objective The aim of this study was to investigate the delivery of Cucurbitacin BE to cervical lymph nodes by peri-cancer submucosal injection of the average diameter 85nm Cucurbitacin BE polylactic acid nanoparticles (CuBE-PLA-NP).Methods Cervical lymph node metastasis model of mice oral cancer was established and CuBE-PLA-NP and CuBE were injected in pericancer submucosal of the mice respectively, the concentration in blood?heart?liver?spleen?lung?kidney and cervical lymph node were measured by high performance liquid chromatography at fifteen time points, Targeted cervical lymph nodes were evaluated by targeting index, selectivity index, targeting efficiency, relative targeting efficiency and ratio of maximum concentration.Results (1)The CuBE concentration in the cervical lymph nodes after CuBE-PLA-NP injection was far higher than that after CuBE injection at every time point, the CuBE duration in the cervical lymph nodes in CuBE-PLA-NP group was far longer than that in CuBE group;(2)The five targeted values of the cervical lymph nodes in CuBE-PLA-NP group was far higher than that in CuBE group;(3)The CuBE concentration in blood?heart?liver?spleen?lung and kidney in CuBE-PLA-NP group was far lower than that in CuBE group.Conclusion The CuBE-PLA-NP can specifically deliver CuBE to the cervical lymph nodes by pericancer submucosal injection, increase CuBE concentration and duration in metastasized cervical lymph nodes, and decrease drug concentration of other organs.