Nanoparticles are increasing in use as drug delivery carries (DDCs) due to their high surface area, tailored surface functionalization, and ability to be excreted. Small particles of like surface charge have been shown to display repulsive tendencies; but at physiologically relevant pH, these same particles form a double layer enabling particle stability. The electrostatic and magnetic forces are beneficial in the exploitation of homogenate and stable DDCs; however, when placed in biofluids, these forces are disturbed. When nanometer-sized DDCs travel through the body to their target site, they encounter many different aqueous environments which alters colloidal stability. We hypothesize that nanoparticle DDCs will become increasingly unstable as the physiologically-relevant fluid for which they are exposed becomes increasing complex. Specifically, the stability of the nanoparticles will be directly related to (1) the alteration in pH from pH 7.0, (2) the concentration of proteins in the biofluid, and (3) the ionic strength of the surrounding matrix. To test this hypothesis, we compared three different surface-functionalized silver nanoparticles coated with positive, negative, and neutral surface charge and characterized through electron microscopy and spectroscopic techniques. Each particle system was incubated in different physiologically-relevant environments: acidic stomach fluid, neutral blood serum, and basic surfactant fluid. To compare inorganic particles against organic particle-types, polymeric-based liposomes were synthesized on the nanometer size scale and subjected them to the same conditions. The next step in this project is to simulate nanoparticle exposure to fluids sequentially using multiple physiologically-relevant conditions. The information obtained from these studies will provide crucial insight into colloidal stability of DDCs, provide read-across comparisons between metal-based and polymeric-based nanoparticles, and aid in filling the literature gap in DDCs colloidal stability affect to nanoparticle biotransformation, <i>in situ</i>.

Development of a chemi-assay battery for nanoparticle biotransformation

2019 Spring National Meeting

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