Assay Cascade

To view the Assay Cascade Protocols, click here.

The Nanotechnology Characterization Laboratory has developed a standardized analytical cascade that tests the preclinical toxicology, pharmacology, and efficacy of nanoparticles and devices. The NCL characterizes nanomaterials from academia, government, and industry, and will help transition them from the discovery-phase into clinical trials. NCL will work with the sponsor to help meet regulatory requirements for an Investigational New Drug (IND) or Investigational Device Exemption (IDE) filing with the FDA. NCL preclinical characterization, including physicochemical, in vitro, and in vivo characterization experiments, is available free-of-charge to accepted proposals, and NCL data can be used in regulatory filings, in publications, and to garner interest from investors.

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 IND or IDE application with the FDA.

Physical Characterization
Physical attributes such as size and ligand distribution, surface characteristics, composition, purity, and stability are key factors contributing to a nanomaterial’s in vivo behavior and tolerability. The first phase of the assay cascade therefore focuses 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 is also addressed during this stage.

In Vitro Characterization
Traditional in vitro biochemical analyses and cell-based assays can mimic the in vivo physiologic environment, addressing biological activity and toxicity issues. The NCL in vitro assay cascade is designed for quick evaluation of nanoparticles prior to the more cost- and labor-intensive in vivo studies. After the initial characterization of nanomaterials to assess their purity and functionality, their safety and efficacy are tested in vitro. The NCL in vitro cascade assesses binding and internalization of nanomaterials, blood contact properties such as coagulation, plasma protein binding, hemolysis, platelet aggregation, etc.

In Vivo Characterization
NCL animal studies are designed to support the Pharmacology and Toxicology section of an IND. NCL performs non-GLP* animal studies in rodents to determine toxicity, ADME (absorption, distribution, metabolism and excretion) profiles, and establish the efficacy of nanomaterial formulations. NCL toxicology studies provide preliminary identification of target organs of acute toxicity and may aid in the selection of starting doses for Phase I human trials. NCL ADME and pharmacokinetic (PK) studies track the various components of a nanoparticle formulation in blood and tissues and may help determine the route of clearance and tissue residence times. NCL efficacy studies utilize transgenic, orthotopic or xenograft tumor models to provide independent verification of collaborators’ proof-of-concept studies.

*According to recent ICH guidelines, a non-GLP Single-Dose Acute Toxicity Study may be utilized in an IND/IDE filing with the US FDA, in conjunction with a GLP Repeat-Dose Acute Toxicity Study.

To view the Assay Cascade Protocols, click here.

To view a list of NCL Instrumentation used for both the chemical and biological characterization of nanomaterials, click here.