title: Theranostic nanoemulsions for macrophage COX-2 inhibition in a murine inflammation model.
abstract: Targeting macrophages for therapeutic and diagnostic purposes is an attractive approach applicable to multiple diseases. Here, we present a theranostic nanoemulsion platform for simultaneous delivery of an anti-inflammatory drug (celecoxib) to macrophages and monitoring of macrophage migration patterns by optical imaging, as measurement of changes in inflammation. The anti-inflammatory effect of the theranostic nanoemulsions was evaluated in a mouse inflammation model induced with complete Freund's adjuvant (CFA). Nanoemulsions showed greater accumulation in the inflamed vs. control paw, with histology confirming their specific localization in CD68 positive macrophages expressing cyclooxygenase-2 (COX-2) compared to neutrophils. With a single dose administration of the celecoxib-loaded theranostic, we observed a reduction in fluorescence in the paw with time, corresponding to a reduction in macrophage infiltration. Our data strongly suggest that delivery of select agents to infiltrating macrophages can potentially lead to new treatments of inflammatory diseases where macrophage behavior changes are monitored in vivo.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282, USA.
authors.forename: Sravan Kumar
authors.initials: SK
authors.lastname: Patel
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
authors.forename: Wissam
authors.initials: W
authors.lastname: Beaino
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15219, USA.|Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15219, USA.|Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.affiliation: Graduate School of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282, USA.|Chronic Pain Research Consortium, Duquesne University, Pittsburgh, PA, 15218, USA.
authors.forename: Jelena M
authors.initials: JM
authors.lastname: Janjic
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000068579:Celecoxib / Q000008:administration & dosage*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004655:Emulsions; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D036103:Nanotechnology / Q000379:methods*; D009504:Neutrophils / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D004655:Emulsions; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C077623:Ptgs2 protein, mouse
keywords: Cyclooxygenase-2; Fluorescence; Imaging; Inflammation; Macrophage