title: Multiscale benchmarking of drug delivery vectors.
abstract: 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.
authors.affiliation: College of Engineering, Swansea University, UK. Electronic address: h.d.summers@swansea.ac.uk.
authors.forename: Huw D
authors.initials: HD
authors.lastname: Summers
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA. Electronic address: Matthew.Ware@bcm.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ware
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA.
authors.forename: Ravish
authors.initials: R
authors.lastname: Majithia
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA. Electronic address: k.meissner@swansea.ac.uk.
authors.forename: Kenith E
authors.initials: KE
authors.lastname: Meissner
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA. Electronic address: bgodin@houstonmethodist.org.
authors.forename: Biana
authors.initials: B
authors.lastname: Godin
authors.affiliation: College of Engineering, Swansea University, UK. Electronic address: p.rees@swansea.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Rees
mesh_terms: D019985:Benchmarking; D016503:Drug Delivery Systems; D005347:Fibroblasts; D005822:Genetic Vectors; D006801:Humans; D053758:Nanoparticles; D011094:Polyethyleneimine; D012822:Silicon Dioxide
chemical_list: D012822:Silicon Dioxide; D011094:Polyethyleneimine
keywords: Dose–Response assays; Drug delivery; Nanomedicine; Nanoparticles; Nanotoxicology