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During this century, several investigators reported that certain viruses, metals, drugs, and other solutes could bypass systemic circulation and enter the brain and/or cerebrospinal fluid directly following nasal administration. Although evidence clearly suggests that the olfactory epithelium and its olfactory cells play a major role, little is known about(More)
AIM The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). METHODS In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3(More)
PURPOSE The purpose of this study was to determine whether budesonide inhibits expression of vascular endothelial growth factor (VEGF) in a retinal pigment epithelial cell line (ARPE-19) and to determine whether subconjunctivally administered budesonide nano- and microparticles sustain retinal drug levels. METHODS The effect of budesonide (100 pM to 10(More)
Despite numerous scientific efforts, delivery of therapeutic amounts of a drug to the retina remains a challenge. This challenge is compounded if chronic therapy is desired. The inability or inefficiency of topical and systemic routes for retinal delivery of existing drugs is now widely accepted. Although the intravitreal route offers high local(More)
OBJECTIVE The aim of the study is to evaluate the effect of nanoparticle-mediated gene delivery of angiogenic inhibitors on retinal inflammation, vascular leakage, and neovascularization in diabetic retinopathy. RESEARCH DESIGN AND METHODS An expression plasmid of plasminogen kringle 5 (K5), a natural angiogenic inhibitor, was encapsulated with(More)
Vascular endothelial growth factor (VEGF), a cytokine expressed in the respiratory epithelial cells, induces vascular hyperpermeability and edema, symptoms that are alleviated by budesonide, an anti-asthma corticosteroid. However, modulation of VEGF levels by budesonide in the respiratory epithelium has not been studied. In this study, we investigated the(More)
Overexpression of vascular endothelial growth factor (VEGF) is implicated in the development of vascular leakage and retinal neovascularization in diabetic subjects. The objective of this study was to determine whether celecoxib, a selective cyclooxygenase-2 enzyme inhibitor, reaches ocular tissues following oral administration and inhibits the retinal VEGF(More)
PURPOSE To determine the influence of the choroid-Bruch's layer and solute lipophilicity on in vitro transscleral drug permeability in bovine and porcine eyes. METHODS The in vitro permeability of two VEGF inhibitory drugs, budesonide and celecoxib, which are lipophilic and neutral at physiologic pH, and of three marker solutes, 3H-mannitol (hydrophilic,(More)
A light-activated polycaprolactone dimethacrylate (PCM) and hydroxyethyl methacrylate (HEMA) based gel network was developed to sustain the release of stable, active bevacizumab (an anti-VEGF antibody used to treat choroidal neovascularization) and used to assess sustained ex vivo delivery in rabbit eyes and in vivo delivery in rat eyes following in situ(More)
Chronic hypoxia, a key stimulus for neovascularization, has been implicated in the pathology of proliferative diabetic retinopathy, retinopathy of prematurity, and wet age related macular degeneration. The aim of the present study was to determine the effect of chronic hypoxia on drug transporter mRNA expression and activity in ocular barriers.(More)