title: Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects.
abstract: Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA.
authors.forename: Soroush
authors.initials: S
authors.lastname: Ardekani
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Scott
authors.affiliation: Department of Physics and Astronomy, University of California, Riverside, CA.
authors.forename: Sharad
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA.
authors.forename: Shane
authors.initials: S
authors.lastname: Eum
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Brunelle
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wilson
authors.affiliation: Department of Physics and Astronomy, University of California, Riverside, CA.
authors.forename: Umar
authors.initials: U
authors.lastname: Mohideen
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA.
authors.forename: Kaustabh
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008081:Liposomes; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D013481:Superoxides / Q000378:metabolism; D020298:U937 Cells; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008081:Liposomes; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D005996:Nitroglycerin