Can histamine cause an enhancement of the cellular uptake and cytotoxicity of doxorubicin-loaded polylactide nanoparticles?

Abstract

Histamine (His) in humans is physiologically involved in neurotransmission and increases vascular permeability during the development of inflammatory response and immunity. It could be used to enhance drug-loaded nanoparticles (NPs) distribution. However, it cannot be freely delivered due to the risk of His-dose-dependent deleterious effects. His can be attached to the polymeric backbone during polymerization to overcome this limitation. In this study, His was used as an initiator of lactide polymerization, and the obtained macromolecules were subsequently used to prepare doxorubicin (DOX)-loaded NPs by nanoprecipitation and microfluidics for examination of anti-cancer properties. Notably, the in vitro activity towards gastric cancer cells (AGS) of the NPs composed of histamine-functionalized polylactides (PLAs) was greatly enhanced compared to control NPs built from hydroxy‑functionalized PLAs. Furthermore, Zonula occludens-1 (ZO-1) tight junction protein production was significantly diminished after treating cells with DOX-loaded NPs assembled with PLAs with histamine residues. These results demonstrate the synergistic effect in cytotoxicity towards gastric cancer cells of DOX and the histamine that are carried by NPs. It is believed that His-DOX NPs strategy may lead to effective, targeted, and low-toxic delivery of drugs into cancer cells.

• Authors: M Brzeziński, W Gonciarz, B Kost, M Chmiela
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 185 Pg. 106438 (Jun 01 2023) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 37001569 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier B.V.

Chemical References

• poly(lactide)
• Histamine
• Doxorubicin

Topics

• Humans
• Histamine
• Stomach Neoplasms (drug therapy)
• Doxorubicin (chemistry)
• Cell Line, Tumor
• Nanoparticles (chemistry)
• Drug Delivery Systems (methods)