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Updated: May 26, 2025
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Published on: January 26, 2024
Development of an intranodal drug delivery system using a mouse model with lymphadenopathy: novel discoveries and
Tetsuya Kodama1,2, Ariunbuyan Sukhbaatar1,2,3
1Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
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.
Insights
The lymphatic drug delivery system (LDDS) improves anticancer drug delivery to lymph nodes (LNs) by direct injection. This review covers LDDS development and its clinical application for head and neck cancer.
Area of Science:
- Oncology
- Pharmacology
- Surgical Innovation
Background:
- Systemic chemotherapy has a low drug delivery rate to metastatic lymph nodes (LNs) due to factors like tumor growth and increased intranodal pressure.
- The lymphatic drug delivery system (LDDS) offers a direct method to inject anticancer drugs into LNs, potentially overcoming these limitations.
Purpose of the Study:
- To review the development of the LDDS from its inception to current clinical trials.
- To discuss the preclinical and clinical applications of LDDS for head and neck cancer treatment.
Main Methods:
- Review of literature on LDDS development, including preclinical studies using the MXH10/Mo-lpr/lpr mouse model.
- Examination of the clinical application of LDDS in head and neck cancer, with the first specific clinical study initiated in Japan in 2024.
Main Results:
- LDDS allows direct drug injection into LNs, bypassing systemic circulation limitations.
- Development focuses on optimizing solvent and injection techniques for uniform drug distribution within LNs.
Conclusions:
- The LDDS represents a novel approach to enhance drug delivery to metastatic lymph nodes.
- Ongoing clinical studies are evaluating the efficacy and safety of LDDS for head and neck cancers.
