Pharmacy and Pharmaceutical Sciences Commons^™

Copper Oxide Nanoparticle Diameter Mediates Serum-Sensitive Toxicity In Beas-2b Cells, Angie S. Morris, Brittany E. Givens, Aaron Silva, Aliasger K. Salem

Chemical and Materials Engineering Faculty Publications

Copper oxide (CuO) nanoparticles (NPs) are abundant in manufacturing processes, but they are an airway irritant. In vitro pulmonary toxicity of CuO NPs has been modeled using cell lines such as human bronchial epithelial cell line BEAS-2B. In 2D in vitro culture, BEAS-2B undergoes squamous differentiation due to the presence of serum. Differentiation is part of the repair process of lung cells in vivo that helps to preserve the epithelial lining of the respiratory tract. Herein, the effects of serum on the hydrodynamic diameter, cellular viability, cellular differentiation, and cellular uptake of 5 and 35 nm CuO NPs are investigated, …

Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO₂ nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more …

Formulation Strategies To Enhance Solubility And Permeability Of Small Molecules For Drug Delivery Applications, Pradeep Kumar Bolla

Open Access Theses & Dissertations

All the new chemical entities/drug molecules intended for therapeutic use must be administered using an appropriate delivery system/dosage form to achieve maximum bioavailability. However, designing a drug delivery system is complex as several factors such as lipophilicity, molecular mass, crystallinity, ionic charge, polymorphic forms and hydrogen bonding) affect the solubility and permeability of these molecules. Biopharmaceutics drug classification system (BCS) categorizes the existing drugs into four classes based on the aqueous solubility and membrane permeability and it is reported that >70% of the drugs are poorly soluble and belong to BCS class II and BCS class IV. Several physical, chemical …

Binding, Transcytosis And Biodistribution Of Anti-Pecam-1 Iron Oxide Nanoparticles For Brain-Targeted Delivery, Mo Dan, David B. Cochran, Robert A. Yokel, Thomas D. Dziubla

Pharmaceutical Sciences Faculty Publications

OBJECTIVE: Characterize the flux of platelet-endothelial cell adhesion molecule (PECAM-1) antibody-coated superparamagnetic iron oxide nanoparticles (IONPs) across the blood-brain barrier (BBB) and its biodistribution in vitro and in vivo.

METHODS: Anti-PECAM-1 IONPs and IgG IONPs were prepared and characterized in house. The binding affinity of these nanoparticles was investigated using human cortical microvascular endothelial cells (hCMEC/D3). Flux assays were performed using a hCMEC/D3 BBB model. To test their immunospecificity index and biodistribution, nanoparticles were given to Sprague Dawley rats by intra-carotid infusion. The capillary depletion method was used to elucidate their distribution between the BBB and brain parenchyma.

RESULTS: Anti-PECAM-1 …

Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and …