1. Establish and Standardize an Analytical Cascade for
Nanomaterial Characterization
Nanomaterials characterized by the NCL are intended for in vivo diagnostic and therapeutic purposes. To this end, the NCL will develop and perform a standardized analytical cascade that tests the pre-clinical toxicology, pharmacology, and efficacy of nanoparticles and devices. Nanomaterials received from academia, government, and industry will be subjected to this
assay cascade that characterizes nanoparticles' physical attributes, their in vitro biological properties, and their in vivo compatibility. 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. This sequence is shown in Figure 1.
Physical Characterization
Current research on therapeutic and diagnostic applications for nanomaterial is helping to identify critical parameters for the material's compatibility with biological systems. Extant literature implicates physical attributes such as size, hydrophilicity, and surface chemistry as key factors contributing to nanomaterial's in vivo fate. The first phase of the analytical cascade will therefore focus on the characterizing of the material's physical properties. The goal of this phase is to determine 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. NCL will rely heavily on the expertise and resources of the NIST for the physical characterization phase.
In Vitro Characterization
Prior to filing an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application with the FDA, a new product must be adequately studied. For these products, toxicity or biocompatibility must first be characterized in animals and efficacy may be standardized in animal discovery models. The cost- and labor-intensiveness of these in vivo studies impel drug and device discovery efforts to utilize in vitro methodologies wherever technology permits. Refined in vitro protocols related to drug and device discovery allow researchers to make a first-order assessment of a material's in vivo pharmacokinetics, biocompatibility, and toxicity.
Nanoparticles' binding, pharmacology, and uptake properties, for example, will be monitored by common cell and molecular biology methods, such as ELISA and fluorescence microscopy. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) will also be used as tools to observe the particle's interaction with cellular-level...
In vitro models can also serve as a gross approximation of a nanomaterial's absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) properties. For example, an initial assessment of acute toxicity can be conducted using hepatic microsomes, primary bone marrow cultures (GM-CFU), or mitochondrial toxicity assays. Other cellular assays to monitor apoptosis and cytotoxicity are now commonplace. As an example of pharmacokinetic characterization, release curves from nanoparticles with drug delivery strategies will be obtained and then assessed against other standardized release models, such as insulin.
