Study of the physicochemical properties of drugs suitable for administration using a lymphatic drug delivery system

Ryoichi Fukumura, Ariunbuyan Sukhbaatar, Radhika Mishra, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

Research output: Contribution to journalArticlepeer-review

Abstract

Lymph node (LN) metastasis is thought to account for 20-30% of deaths from head and neck cancer. The lymphatic drug delivery system (LDDS) is a new technology that enables the injection of drugs into a sentinel LN (SLN) during the early stage of tumor metastasis to treat the SLN and secondary metastatic LNs. However, the optimal physicochemical properties of the solvent used to carry the drug have not been determined. Here, we show that the osmotic pressure and viscosity of the solvent influenced the antitumor effect of cisplatin (CDDP) in a mouse model of LN metastasis. Tumor cells were inoculated into the proper axillary LN (PALN), and the LDDS was used to inject CDDP solution into the subiliac LN (SiLN) to treat the tumor cells in the downstream PALN. CDDP dissolved in saline had no therapeutic effects in the PALN after it was injected into the SiLN using the LDDS or into the tail vein (as a control). However, CDDP solution with an osmotic pressure of ~ 1,900 kPa and a viscosity of ~ 12 mPa⋅s suppressed tumor growth in the PALN after it was injected into the SiLN using the LDDS. The high osmotic pressure dilated the lymphatic vessels and sinuses to enhance drug flow in the PALN, and the high viscosity increased the retention of CDDP in the PALN. Our results demonstrate that optimizing the osmotic pressure and viscosity of the solvent can enhance the effects of CDDP, and possibly other anticancer drugs, after administration using the LDDS.

Original languageEnglish
JournalCancer science
DOIs
Publication statusAccepted/In press - 2021
Externally publishedYes

Keywords

  • cisplatin
  • lymph node metastasis
  • lymphatic drug delivery system
  • osmotic pressure
  • viscosity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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