Intralymphatic injection of chemotherapy drugs modulated with glucose improves their anticancer effect

Ariunbuyan Sukhbaatar; Shiro Mori; Kiyoto Shiga; Tetsuya Kodama

doi:10.1016/j.biopha.2023.115110

Intralymphatic injection of chemotherapy drugs modulated with glucose improves their anticancer effect

Biomed Pharmacother. 2023 Sep:165:115110. doi: 10.1016/j.biopha.2023.115110. Epub 2023 Jul 6.

Authors

Ariunbuyan Sukhbaatar¹, Shiro Mori¹, Kiyoto Shiga², Tetsuya Kodama³

Affiliations

¹ Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Division of Oral and Maxillofacial Oncology and Surgical Sciences, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.
² Department of Head and Neck Surgery, Iwate University Hospital, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan.
³ Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan. Electronic address: kodama@tohoku.ac.jp.

PMID: 37421779
DOI: 10.1016/j.biopha.2023.115110

Abstract

Lymph node metastasis (LNM) has a significant impact on cancer prognosis, emphasizing the need for effective treatment strategies. This study investigated the potential use of high osmotic pressure drug solutions with low viscosity administration using a lymphatic drug delivery system (LDDS) to improve LNM treatment outcomes. The hypothesis was that injection of epirubicin or nimustine at high osmotic pressure but without altered viscosity would enhance drug retention and accumulation in LNs, thereby improving the efficacy of treatment. Biofluorescence analysis revealed enhanced drug accumulation and retention in LNs after administration using LDDS compared to intravenous (i.v) injection. Histopathological results demonstrated minimal tissue damage in the LDDS groups. Pharmacokinetic analysis revealed an improved treatment response with higher drug accumulation and retention in LNs. The LDDS approach offers the potential for greatly reduced side effects of chemotherapy drugs, lower dosage requirements and crucially increased drug retention in LNs. The results highlight the promise of high osmotic pressure drug solutions with low viscosity administrated using the LDDS for enhancing the treatment efficacy of LN metastasis. Further research and clinical trials are warranted to validate these results and optimize the clinical translation of this novel treatment technique.

Keywords: Chemotherapy; Epirubicin; Lymph node metastasis; Lymphatic drug delivery; Nimustine; Osmotic pressure.

MeSH terms

Drug Delivery Systems / methods
Glucose* / pharmacology
Humans
Injections
Injections, Intralymphatic
Lymph Nodes*
Lymphatic Metastasis / pathology

Substances

Glucose