Akamo Y, Yotsuyanagi T, Mizuno I, Ichino T, Tanimoto N, Kurahashi S, Saito T, Yamamoto T, Yasui T, Itabashi Y
First Department of Surgery, Nagoya City University Medical School.
Jpn J Cancer Res. 1993 Feb;84(2):208-13. doi: 10.1111/j.1349-7006.1993.tb02857.x.
We investigated the feasibility of specifically delivering adriamycin (ADR) to the regional lymph nodes via gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in a rabbit model. We determined the tissue distribution of ADR for up to 7 days after the gastric submucosal injection of Lipo-ADR (0.4 mg/kg of ADR potency) and i.v. administration of an equal dose of free adriamycin (F-ADR). The area under the ADR concentration-time curve (AUC) of the regional lymph nodes was 85.4 micrograms.day/g after gastric submucosal injection of Lipo-ADR and 8.44 micrograms.day/g after i.v. administration of F-ADR. The targeting index of the regional lymph nodes, defined as the ratio of the AUC after gastric submucosal injection of Lipo-ADR to the AUC after i.v. administration of F-ADR, was 10.1. Gastric submucosal injection of Lipo-ADR enhanced lymph node-specific delivery of ADR compared with i.v. administration of F-ADR. The targeting index was 0.47 for the heart, 0.25 for the bone marrow, and 0.41 for the spleen, indicating that gastric submucosal injection of Lipo-ADR reduced delivery of ADR to these organs, as compared with i.v. administration of F-ADR. These data demonstrate that gastric submucosal injection of Lipo-ADR is well suited for specific delivery of ADR to the regional lymph nodes, suggesting that this method of administration may be useful in delivering preoperative adjuvant chemotherapy for preventing gastric cancer recurrence.
我们在兔模型中研究了通过胃黏膜下注射脂质体阿霉素(Lipo-ADR)将阿霉素(ADR)特异性递送至区域淋巴结的可行性。我们测定了胃黏膜下注射Lipo-ADR(阿霉素效价为0.4mg/kg)和静脉注射等量游离阿霉素(F-ADR)后长达7天的阿霉素组织分布情况。胃黏膜下注射Lipo-ADR后区域淋巴结的阿霉素浓度-时间曲线下面积(AUC)为85.4μg·天/g,静脉注射F-ADR后为8.44μg·天/g。区域淋巴结的靶向指数定义为胃黏膜下注射Lipo-ADR后的AUC与静脉注射F-ADR后的AUC之比,为10.1。与静脉注射F-ADR相比,胃黏膜下注射Lipo-ADR增强了阿霉素向淋巴结的特异性递送。心脏的靶向指数为0.47,骨髓为0.25,脾脏为0.41,这表明与静脉注射F-ADR相比,胃黏膜下注射Lipo-ADR减少了阿霉素向这些器官的递送。这些数据表明,胃黏膜下注射Lipo-ADR非常适合将阿霉素特异性递送至区域淋巴结,提示这种给药方法可能有助于术前辅助化疗以预防胃癌复发。