Vivien Nagy, Már Másson and Sabina Quader
N,N,N-Trimethyl chitosan (TMC) is a chitosan derivative with significant antibacterial activity and enhanced aqueous solubility compared to unmodified chitosan. This study investigated the relationship between cytotoxicity, degree of trimethylation (DTM), and molecular weight (Mw) across five distinct TMC samples. Additionally, polyelectrolyte complex nanoparticles (NPs) were prepared using TMC and chondroitin sulfate (ChS).
The size and PDI of the NPs were measured by dynamic light scattering (DLS) method. The cytotoxicity of TMC and TMC-ChS NPs was investigated against human umbilical vein endothelial cells (HUVECs) and two human ovarian carcinoma cell lines (OVISE, SKOV-3).
The TMC sample with the highest DTM (99%) was found most toxic in HUVECs, followed by the second and the third highest DTMs, 48% and 46%, respectively. Regarding the Mw, the following trend was observed: decreasing Mw results in increasing toxicity against HUVECs, except for the TMC with 99% DTM (290 kDa), suggesting that both the DTM and the Mw of the sample influence the toxicity. The TMC samples displayed greater cytotoxicity towards SKOV-3 and OVISE cancer cells compared to HUVECs. Remarkably, TMC-ChS NPs exhibited significantly reduced cytotoxicity across all tested cells.
The cytotoxicity of TMC and the TMC-ChS NPs was investigated, and the results suggested that both DTM and Mw affect the toxicity, with the relationship also dependent on cell type. In general, the TMC samples exhibited heightened toxicity towards cancer cells compared to HUVECs. Additionally, NP formation decreased the toxicity towards all the studied cells, underscoring the toxicity-mitigating potential of NP formation.
