(598c) In Vitro Assay for the Release Kinetics of Hydrophobic Drugs From Nanoparticle Carriers

The release kinetics of hydrophobic drugs from nanoparticle carriers are not well understood because the standard protocols for maintaining sink conditions and sampling for traditional dosage forms are not valid due to mass transfer and solubility limitations (S. Petersen, A. Fahr, H. Bunjes. Molecular Pharmaceutics. 2010). We present a new in vitro assay protocol based on ?sink particles? and magnetic separations that enable the formulation of release media that mimics the high concentrations of lipid membranes and lipoproteins in vivo, facilitates separation, and thus allows the determination of intrinsic release rates of drugs from nanoparticles in circulation. To accomplish this, stable lipid microparticles that encapsulate superparamagnetic CoFeO₃ nanoparticles have been formulated to serve as high surface area, hydrophobic sinks for drugs released from nanoparticles. These lipid particles are incubated with nanoparticles and, by subjecting aqueous samples to high gradient magnetic fields, the lipid particles are isolated from the nanoparticles. The separated fractions are then assayed for drug concentration to construct a release profile. Tracking the release rates of hydrophobic fluorescent compounds, we have determined the intrinsic release rates and shown that the release rates may be controlled by the morphology of the drug nanoparticle core. The release profile for itraconazole, a hydrophobic antifungal drug, from a polymer stabilized nanoparticle has been determined. This system provides promising route to improve the efficiency of nanocarrier development and evaluation prior to in vivo testing.