title: Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses.
abstract: Liposomes are phospholipid nanoparticles used for targeted drug delivery. This study aimed to determine whether intravenous liposomes accumulate in lamellar tissue during laminitis development in horses so as to assess their potential for targeted lamellar drug delivery. Polyethylene-glycol (PEG) coated liposomes were prepared according to the film hydration method and labelled using (99m)Tc-hexamethyl-propylene-amine-oxime. Six horses received 10 g/kg oligofructose via nasogastric tube to induce laminitis, and four control horses received water via nasogastric tube. All horses received 300 µmol (99m)Tc-PEG-liposomes (5.5 GBq) plus 5.5 µmol/kg PEG-liposomes by slow intravenous infusion. Scintigraphic imaging was performed at 0, 6 and 12 h post-infusion. Technetium-99m liposome uptake was measured in regions of interest over the hoof, fetlock and metacarpus. At the study end-point horses were euthanased, tissue samples collected and tissue liposome levels were calculated as the percentage of the injected dose of (99m)Tc-liposomes per kilogram of tissue. Data were analysed non-parametrically. All horses receiving oligofructose developed clinical and histological signs of laminitis. Technetium-99m liposome uptake in the hoof increased with time in laminitis horses (P = 0.04), but decreased with time in control horses (P = 0.01). Technetium-99m liposome levels in lamellar tissue from laminitis horses were 3.2-fold higher than controls (P = 0.02) and were also higher in laminitis vs. control skin, muscle, jejunum, colon, and kidney (P < 0.05). Liposomes accumulated in lamellar tissue during oligofructose-induced laminitis development and demonstrated potential for targeted lamellar drug delivery in acute laminitis. This study provides further evidence that lamellar inflammation occurs during laminitis development. Liposome accumulation also occurred in the skin, muscle, jejunum, colon and kidneys, suggesting systemic inflammation in this model.
authors.affiliation: Australian Equine Laminitis Research Unit, School of Veterinary Science, University of Queensland, Gatton, QLD 4343, Australia. Electronic address: c.underwood1@uq.edu.au.
authors.forename: Claire
authors.initials: C
authors.lastname: Underwood
authors.affiliation: Australian Equine Laminitis Research Unit, School of Veterinary Science, University of Queensland, Gatton, QLD 4343, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Pollitt
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
authors.forename: Josbert M
authors.initials: JM
authors.lastname: Metselaar
authors.affiliation: Radboud University Medical Centre Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), University of Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: van Bloois
authors.affiliation: Department of Pharmacy and Pharmacology, Sloterevaart Hospital, Amsterdam, The Netherlands.
authors.forename: Jolanda M
authors.initials: JM
authors.lastname: van den Hoven
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), University of Utrecht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Australian Equine Laminitis Research Unit, School of Veterinary Science, University of Queensland, Gatton, QLD 4343, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: van Eps
mesh_terms: D000818:Animals; D005534:Foot Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000662:veterinary*; D006724:Hoof and Claw / Q000473:pathology; D006734:Horse Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging; D006736:Horses; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000662:veterinary; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D009844:Oligosaccharides / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D019690:Technetium Tc 99m Exametazime / Q000493:pharmacokinetics*
chemical_list: D008081:Liposomes; D009844:Oligosaccharides; D019275:Radiopharmaceuticals; C120489:oligofructose; D019690:Technetium Tc 99m Exametazime; D011092:Polyethylene Glycols
keywords: Horse; Liposome; Nanoparticle; Nanotechnology; Scintigraphy