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

Ryoichi Fukumura1,2, Ariunbuyan Sukhbaatar1,2, Radhika Mishra1,2

  • 1Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.

Cancer Science
|February 25, 2021
PubMed

Insights

Optimizing solvent properties like osmotic pressure and viscosity enhances lymphatic drug delivery system (LDDS) effectiveness for treating head and neck cancer metastasis in lymph nodes (LNs). This approach improves cisplatin delivery and antitumor effects.

Area of Science:

  • Oncology
  • Drug Delivery Systems
  • Cancer Metastasis Research

Background:

  • Lymph node (LN) metastasis is a major cause of mortality in head and neck cancers.
  • The lymphatic drug delivery system (LDDS) offers a novel approach for early-stage cancer treatment by targeting sentinel lymph nodes (SLNs).
  • Optimal physicochemical properties of drug solvents for LDDS remain undetermined.

Purpose of the Study:

  • To investigate the influence of solvent osmotic pressure and viscosity on the efficacy of cisplatin (CDDP) delivered via LDDS in a mouse model of lymph node metastasis.
  • To determine the ideal physicochemical properties for solvents used in LDDS for enhanced antitumor effects.

Main Methods:

  • A mouse model of lymph node metastasis was established by inoculating tumor cells into the proper axillary lymph node (PALN).
  • CDDP was administered using LDDS into the subiliac lymph node (SiLN) to target the downstream PALN.
  • Different CDDP solutions, including saline and optimized formulations (approx. 1,900 kPa osmotic pressure, 12 mPa·s viscosity), were tested.

Main Results:

  • CDDP in saline showed no therapeutic effect in the PALN, regardless of administration route (LDDS or intravenous).
  • CDDP formulated with high osmotic pressure (~1,900 kPa) and viscosity (~12 mPa·s) significantly suppressed tumor growth in the PALN when delivered via LDDS.
  • High osmotic pressure facilitated lymphatic vessel dilation and drug flow, while high viscosity enhanced drug retention in the target lymph node.

Conclusions:

  • Solvent osmotic pressure and viscosity are critical factors influencing the efficacy of CDDP delivered via LDDS.
  • Optimized physicochemical properties of the solvent can significantly enhance the antitumor effects of CDDP and potentially other drugs administered through LDDS.
  • This study provides a foundation for developing improved drug formulations for lymphatic drug delivery in cancer treatment.
Keywords:
cisplatinlymph node metastasislymphatic drug delivery systemosmotic pressureviscosity

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