NCL-02: Nanomedicine Pharmacokinetics in Rats Evaluated by SITUA

The Nanotechnology Characterization Laboratory will evaluate the pharmacokinetics of a nanoparticulate formulation in rats using a novel stable isotope tracer ultrafiltration assay (SITUA) developed at the laboratory. The SITUA is a method to fractionate encapsulated and unencapsulated drug (active pharmaceutical ingredient) administered as a nanoparticulate formulation in plasma matrix. Advantages of the method include increased accuracy and precision in comparison to other available methods of assessing nanomedicine release. The measurement of encapsulated and unencapsulated nanomedicine drug fractions as part of a preclinical or clinical pharmacokinetic study is important for understanding the pharmacology of nanoparticulate formulations. The measurement of these fractions has also become increasingly important for establishing the bioequivalence of generic versions of nanomedicines.

After the test sample is administered to double-jugular catheterized rats, blood samples will be drawn at multiple timepoints and prepared immediately for analysis using the SITUA method. The samples will be assessed using an established bioanalytical method, and the resulting data will be used to calculate concentrations of the various nanomedicine fractions, including (a) nanomedicine-encapsulated, (b) unencapsulated free-unbound, and (c) unencapsulated protein-bound. The resulting concentration data will be evaluated using standard noncompartmental pharmacokinetic analysis. The in vivo study design will be presented to the appropriate sponsor personnel prior to study initiation. The animal studies will be conducted in collaboration with the Frederick National Laboratory’s Laboratory Animal Science Program. Sufficient basic consultation with Stephan Stern, Ph.D., senior principal scientist and head of pharmacology and toxicology at the Nanotechnology Characterization Laboratory is included as part of the service to address technical questions regarding the method and results, and to assist with data interpretation. 

More details on the SITUA can be found in the following publications: