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

Abstract

Introduction: The low drug delivery rate of systemic chemotherapyto metastatic lymph nodes (LNs) may be due to tumor growth without tumorneovascularization in the LNs, loss of existing blood vessels and lymph sinusesdue to the tumor growth, and increased intranodal pressure. The lymphatic drugdelivery system (LDDS) is a method of injecting anticancer drugs directly intothe LNs and can overcome these problems. The world's first specific clinicalstudy using the LDDS for head and neck cancer started in 2024 in Japan. In thisreview, the background of the development of LDDS up to the present clinicaltrials is described.

Areas covered: The MXH10/Mo-lpr/lpr(MXH10/Mo/lpr) recombinant inbred model mouse, vascular and lymphatic flowthrough 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 administrationhave been the focus of attention for drug delivery to LNs. The LDDS is a methodfor injecting drugs directly to LNs, so it is important to develop a solventand injecting method that can increase the uniformity of drug distributionwithin LNs.