Osmotic pressure and viscosity: Anticancer drug efficacy and restricting tumors using LDDS (Ranges given to optimize killing cancer cells in lymphatic glands from metastasis)

Chemotherapy is known for its painful side-effects. It also has limitations when the cancer has metastasized to the lymph nodes. The lymphatic drug delivery system (LDDS), where anticancer drugs are injected directly into the sentinel lymph nodes under ultrasound guidance, offers an alternative to conventional chemotherapy. Researchers found the optimal osmotic pressure and viscosity ranges, significantly improving the antitumor effect.

Cancer often transfers from its primary lesion to other lesions—clinically referred to as metastasis. In early metastasis, cancer cells invade lymphatic vessels, reach lymph nodes, and proliferate. Conventional chemotherapy for metastatic lymph nodes has limitations because only part of anticancer drug administrated by intravenous injection reaches the metastatic lymph nodes, and the expanded tumors restrict the bloodstream, preventing anticancer drug delivery.

LDDS provides an alternative strategy to conventional chemotherapy. Anticancer drugs are injected directly into sentinel lymph nodes under ultrasound guidance. LDDS is also available during intra-operative or image-guided surgery.

Professor Tetsuya Kodama investigated the effect of osmotic pressure and the viscosity of anticancer drugs on the efficacy of lymph node metastasis treatment. Optimal osmotic pressure and viscosity ranges significantly improved an antitumor effect.

This improvement could be explained as follows: the hyperosmotic fluid injected into the tumor-draining lymph nodes may increase the inflow of liquid components from blood vessels and high endothelial venules. Anticancer drugs with higher osmotic fluid could also flow in the efferent lymphatic vessels and the case expansion of lymphatic channels and vessels, allowing anticancer drugs to target tumor cells. Moreover, the optimized anticancer drugs of LDDS could target not only sentinel lymph nodes but also downstream lymph nodes with a high risk of secondary metastasis.

In summary, treatment using LDDS optimizes the physical properties of anticancer drugs, osmotic pressure and viscosity; improves the treatment efficacy; and restricts the spread of tumors in lymph node metastasis.

The exact best ranges were given in the study. Please give this information to your doctor, if LDDS can or is being used:

“To improve the survival rate of patients with LN metastasis, a lymphatic drug delivery system (LDDS) has been developed to target metastatic LN by delivering chemotherapy agents into sentinel LN (SLN) under ultrasound guidance. The LDDS is an advanced method that can be applied in the early stage of the progression of tumor cells in the SLN before tumor mass formation has occurred. Here we investigated the optimal physicochemical ranges of chemotherapeutic agents’ solvents with the aim of increasing treatment efficacy using the LDDS. We found that an appropriate osmotic pressure range for drug administration was 700–3,000 kPa, with a viscosity < 40 mPa⋅s. In these physicochemical ranges, expansion of lymphatic vessels and sinuses, drug retention, and subsequent antitumor effects could be more precisely controlled. Furthermore, the antitumor effects depended on the tumor progression stage in the SLN, the injection rate, and the volumes of administered drugs.”

https://onlinelibrary.wiley.com/doi/10.1111/cas.15283

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