Novel Drug Delivery Method Targeting Para-Aortic Lymph Nodes by Retrograde Infusion of Paclitaxel into Pigs' Thoracic Duct.

Abstract

Simple SummaryFor advanced cancer, surgery may not be possible at the site of lymph node metastasis, such as para-aortic lymph node metastasis. Systemic administration of anticancer drugs has been performed in these cases, but treatment results are still inadequate. This study investigated the efficiency of drug delivery to intra-abdominal lymph nodes by administering an anticancer drug retrogradely to lymphatic vessels in order to deliver the drug directly to the metastatic lymph nodes. Thoracic duct infusion resulted in the same concentration of paclitaxel in abdominal lymph nodes as via systemic administration, but the serum concentration was lower. The results show that thoracic infusion may achieve higher paclitaxel doses than systemic administration. Infusion of anti-cancer drugs into the thoracic duct may yield clinical benefits for patients with extensive lymphatic metastases in abdominal malignancies.Gastrointestinal cancer with massive nodal metastases is a lethal disease. In this study, using a porcine model, we infused the anti-cancer drug Paclitaxel (PTX) into thoracic ducts to examine the efficiency of drug delivery to intra-abdominal lymph nodes. We established a technical method to catheterize the thoracic duct in the necks of pigs. We then compared the pharmacokinetics of PTX administered intrathoracically with those of systemic (intravenous) infusion. Serum, liver, and spleen concentrations of PTX were significantly lower following thoracic duct (IT) infusion than after intravenous (IV) administration approximately 1–8 h post-infusion. However, PTX levels in abdominal lymph nodes were maintained at relatively high levels up to 24 h after IT infusion compared to after IV infusion. Concentrations of PTX in urine were much higher after IT administration than after IV administration. After IT infusion, the same concentration of PTX was obtained in abdominal lymph nodes, but the serum concentration was lower than after systemic infusion. Therefore, IT infusion may be able to achieve higher PTX doses than IV infusion. IT delivery of anti-cancer drugs into the thoracic duct may yield clinical benefits for patients with extensive lymphatic metastases in abdominal malignancies.