Multiscale benchmarking of drug delivery vectors

Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo.

Many of the key advances in nanomedicine relate to the concept of delivery of a drug via a secondary carrier - a delivery vector. Here we present an experimental approach that allows quantitative comparison of delivery vectors across scales. This allows detailed analysis and discrimination of the relative roles of the carrier and the drug in determining cell response.127