Overview of Lymphatic Drug Delivery Systems (LDDS) and the Optimal Ranges of Solvent Osmolarity and Viscosity Depending on Therapeutic Strategies.
Illustration Credit: ©Taiki Shimano et al.
Scientific Frontline: "At a Glance" Summary
- Main Discovery: The optimization of solvent osmolarity and viscosity in Lymphatic Drug Delivery Systems (LDDS) significantly regulates drug pharmacokinetics and perinodal dynamics to improve treatment of metastatic lymph nodes.
- Methodology: Researchers injected therapeutic formulations directly into the sentinel lymph nodes of MXH10/Mo/lpr mice—a model featuring human-sized nodes—to monitor real-time changes in lymphatic and vascular flow based on varied solvent properties.
- Key Data: Increased solvent osmolarity was observed to promote blood inflow and expand lymphatic sinuses (drug pathways), while solvent viscosity acted as the dominant factor determining the duration of drug retention and the extent of delivery.
- Significance: The study provides critical guidelines for "tailor-made solvent design," directly validating the protocols for ongoing Phase I clinical trials at Iwate Medical University and Tohoku University Hospital.
- Future Application: Development of next-generation cancer therapies where drug solvent properties are customized to specific clinical goals, such as maximizing retention time or enhancing downstream distribution.
- Branch of Science: Biomedical Engineering, Oncology, and Pharmacology.
- Additional Detail: This research represents the first comprehensive demonstration of how fundamental physicochemical properties of solvents independently influence drug behavior during intranodal administration.
Optimizing drug delivery to the lymphatic system is essential for effective cancer treatment, as lymph node (LN) metastasis is a critical factor influencing patient prognosis.
A research team led by Professor Tetsuya Kodama from the Graduate School of Biomedical Engineering at Tohoku University has published groundbreaking findings that clarify how the physicochemical properties of therapeutic formulations govern lymphatic and vascular flow dynamics.
The study, published in Biomedicine & Pharmacotherapy is the first to comprehensively demonstrate how the osmolarity and viscosity of solvents influence drug behavior during and after administration via a Lymphatic Drug Delivery System (LDDS). In LDDS, anticancer drugs are injected directly into sentinel LNs to reach downstream nodes, serving as an innovative complement to traditional systemic chemotherapy.
To achieve this, the researchers employed MXH10/Mo/lpr mice, a unique animal model characterized by macroscopically enlarged LNs similar in size to those of humans. By precisely controlling the solvent conditions, the team analyzed real-time changes in lymphatic and blood flow.
"We determined that increasing solvent osmolarity promotes blood inflow into the injected LN, leading to the expansion of the lymphatic sinus, which serves as the drug pathway in the LN" explains Kodama. Furthermore, the team clarified that solvent viscosity is the dominant factor determining drug retention and the extent of delivery within the vascular and lymphatic systems.
These findings provide clear guidelines for "tailor-made solvent design" based on specific clinical cases and therapeutic goals. This research directly supports the validity of ongoing Phase I clinical trials currently being conducted at Iwate Medical University and Tohoku University Hospital. This discovery is expected to accelerate the clinical application of LDDS as a next-generation platform for cancer treatment.
Published in journal: Biomedicine & Pharmacotherapy
Authors: Taiki Shimano, Daiki Nagamatsu, Ryoichi Fukumura, Ariunbuyan Sukhbaatar, Shiro Mori, and Tetsuya Kodama
Source/Credit: Tohoku University
Reference Number: bmed012626_01
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