Toxicity and cellular uptake of lipid nanoparticles of different structure and composition

Cubosomes form part of the next generation of lipid nanoparticle drug delivery vehicles, enabling higher drug encapsulation efficiency, particularly for lipophilic drugs, compared to traditional liposome formulations. However, the mechanism of interaction of cubosome lipid nanoparticles with cells and their resultant cytotoxicity is not yet well characterised. We hypothesise that the uptake mechanism is dependent on the cell-type, and that cellular toxicity will be controlled by both the lipid composition and the uptake mechanism. The uptake of cubosomes into fibroblast and macrophage cell lines was investigated using live-cell imaging on a confocal microscope. Toxicity of the lipid particles was determined using Fluorescence-Activated Cell Sorting (FACS). Atomic Force Microscopy (AFM) provided an overview of the topography of the surface of individual cells. The cells exhibited a contrast in uptake kinetics depending on cell type attributed to varying uptake mechanisms. Cellular toxicity was dictated more by lipid composition than by the internal particle nanostructure or the uptake mechanism. Surface topography showed many surface ridges in the STO cells which could provide a location for cubosome adhesion prior to uptake. The findings provide a crucial guideline for the future engineering and application of lipid nanoparticles in drug delivery applications. (C) 2020 Elsevier Inc. All rights reserved.