Assay Cascade

To view the Assay Cascade Protocols, click here.

The National Characterization Laboratory will develop and perform a standardized analytical cascade that tests the pre-clinical toxicology, pharmacology, and efficacy of nanoparticles and devices. The NCL will characterize nanomaterials from academia, government, and industry for their physical attributes, their in vitro biological properties, and their in vivo compatibility through the use of animal models.  The assay cascade is designed to provide data and information related to the nanoparticles’ interaction and compatibility with biological systems.

The time required to characterize a nanoparticle from receipt through the in vivo phase is anticipated to be 1 year, ultimately enabling a sponsor’s filing of an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application with the FDA.

Physical Characterization
Physical attributes such as size, hydrophilicity, and surface chemistry are key factors that contribute to a nanomaterial’s fate in vivo. The first phase of the assay cascade will therefore focus on characterizing the material’s physical properties, including the particle’s size, size distribution, molecular weight, density, surface area, porosity, hydrophilicity, surface charge density, purity, sterility, surface chemistry, and stability. The batch-to-batch reproducibility of material as provided by the sponsor/vendor will also be addressed during this stage.

In Vitro Characterization
Prior to filing an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application with the FDA, a new products’ toxicity or biocompatibility must be adequately studied.  During this characterization, nanoparticles’ binding, pharmacology, and update properties, for example, will be monitored by common cell and molecular biology methods.  Also included in this stage is a characterization of the nanomaterial’s blood contact properties, an observation of the particle’s interaction with cellular-level components, and a thorough examination of the particle’s therapeutic and/or diagnostic functionality.  In vitro models can also serve as a gross approximation of a nanomaterial’s absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties.

In Vivo Characterization
The primary goal of the in vivo characterization is to elucidate the nanomaterial’s safety, efficacy, and toxicokinetic properties in animal models, which must be obtained prior to transitioning the nanoparticles to clinical applications. The phase will leverage the plethora of knowledge and protocols used to characterize drugs and devices in vivo.  Nanoparticles will be administered to animals to identify (1) doses causing no adverse effect and (2) doses causing life-threatening toxicity.  In vivo studies will characterize the nanoparticle’s absorption, pharmacokinetics, serum half-life, protein binding, tissue distribution/accumulation, enzyme inductin or inhibition, metabolism characteristics and metabolites, and excretion pattern.

To view the Assay Cascade Protocols, click here.