Development of an intranodal drug delivery system using a mouse model with lymphadenopathy: novel discoveries and clinical application.

Introduction: The low drug delivery rate of systemic chemotherapy to metastatic lymph nodes (LNs) may be due to tumor growth without tumor neovascularization in the LNs, loss of existing blood vessels and lymph sinuses due to the tumor growth, and increased intranodal pressure. The lymphatic drug delivery system (LDDS) is a method of injecting anticancer drugs directly into the LNs and can overcome these problems. The world's first specific clinical study using the LDDS for head and neck cancer started in 2024 in Japan. In this review, the background of the development of LDDS up to the present clinical trials is described.

Areas covered: The MXH10/Mo-lpr/lpr (MXH10/Mo/lpr) recombinant inbred model mouse, vascular and lymphatic flow through LNs, the clinical N0 (cN0) LN model, preclinical studies of the LDDS, and its clinical application to treat head and neck cancer.

Expert opinion: Conventionally, hematogenous and lymphatic administration have been the focus of attention for drug delivery to LNs. The LDDS is a method for injecting drugs directly to LNs, so it is important to develop a solvent and injecting method that can increase the uniformity of drug distribution within LNs.