Abstract 2005: Optimized range of osmotic pressure and viscosity for a lymphatic drug delivery system

Abstract

Abstract The lymphatic drug delivery system (LDDS) is a method that allows the injection of drugs into sentinel lymph nodes (SLNs) to facilitate their delivery to downstream lymph nodes (LNs) via the lymphatic network to treat or prevent cancer cell development in both LNs. A high concentration of drug is effectively maintained in both LNs. Here we show that therapeutic effects in metastatic LNs depend on the osmotic pressure and viscosity of the administered drug in a metastatic mouse (MXH10/Mo-lpr/lpr) model. We found using an in vivo bioluminescence imaging system that indocyanine (ICG) solutions were retained in the proper axillary lymph node (PALN) at an osmotic pressure > 1,700 kPa and 6 mPa·s viscosity, when ICG solution was injected into the SiLN to deliver it to the (PALN). Edematous swelling was detected near the SiLN at > 3,500 kPa osmotic pressure and 400 mPa·s viscosity. Furthermore, we established that the therapeutic effects of drugs on metastatic PALN were observed in the osmotic pressure range 1000 - 2400 kPa and viscosity range 2 - 30 mPa·s, after tumor cells were injected into the SiLN to induce metastasis in the PALN. Cisplatin solution was injected into the accessory axillary lymph node to deliver cisplatin to the metastatic PALN. Our results demonstrate the optimized values of osmotic pressure and viscosity for LDDS. We anticipate our results to be a starting point for more sophisticated drug administration by a LDDS. Citation Format: Tetsuya Kodama, Shiro Mori. Optimized range of osmotic pressure and viscosity for a lymphatic drug delivery system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2005.