Delivery of Lymph Node‐targeted Adriamycin by Gastric Submucosal Liposomal Injection in Rabbits

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Abstract
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 nag/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 μg‐day/g after gastric submucosal injection of Lipo‐ADR and 8.44 μg‐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.