阿霉素脂质体淋巴管灌注的靶向效果

Targeting Delivery of Liposomal Adriamycin by Intra lymphatic Infusion

目的：探讨阿霉素脂质体经淋巴管灌注后的体内动力学过程以及靶向效果。方法：将６０只家兔随机分为阿霉素脂质体和阿霉素水溶液两组，从家兔足背淋巴管给药，采用高效液相色谱（ＨＰＬＣ）法检测给药后各时点外周血及腹膜后淋巴结中阿霉素药物浓度，并将摘取的淋巴结作病理检查。结果：水溶液组腹膜后淋巴结阿霉素峰浓度（Ｃｍａｘ）为４６．８１μｇ／ｇ，药时曲线下面积（ＡＵＣ）为３１．８６μｇ／ｄａｙｇ－１；而脂质体组阿霉素峰浓度为９１．２３μｇ／ｇ，ＡＵＣ为１３８．３４μｇ／ｄａｙｇ－１。在外周血中脂质体组的峰浓度只有水溶液组的１／５。淋巴结病理检查结果表明，脂质体组的水肿、坏死、纤维化较水溶液组明显，而心肌病理反应较轻或不存在。结论：脂质体对淋巴结具有高度靶向性，阿霉素脂质体淋巴管灌注有可能成为治疗淋巴结转移的有效且副作用少的新方法。

Objective: To assess the feasibility of delivering liposomal adriamycin (lipo ADM) to the regional lymph nodes via intralymphatic infusion in a rabbits model. Methods: The plasma and tissue ADM levels were measured by high performance liquid chromatography (HPLC) at 0.5 hour, 1 hour, 6 hours, 12 hours, 1 day, 7 days, 14 days, 28 days. Results: The maximun ADM level (Cmax) in the lymph nodes of lipo ADM was 91.23 μg/g, which was 2 times higher than that of the free ADM group. The area under the ADM concentration time curve (AUC) of the regional lymph nodes of lipo ADM and free ADM was 138.34 μg/day·g -1 ,31.86 μg/day·g -1 respectively ( P <0.01). The pathological features showed that the lipo ADM group had more microabscess, necrosis and fibrosis in the lymph nodes than those of the free ADM group. The histological changes of heart were absent or slight in the lipo ADM group. Conclusions: lipo ADM has a high affinity for lymphatic tissue. Intralymphatic infusion of lipo ADM may be useful for the treatment of lymphnode metastasis in ovarian cancer.