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.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication Date: 2015-07-20 PubMed ID: 26403954DOI: 10.1016/j.tvjl.2015.07.013Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research paper focuses on the use of liposomes, a type of phospholipid nanoparticle, as potential targeted drug delivery mechanisms in the treatment of laminitis in horses. The study followed how these liposomes accumulated in lamellar tissue during the development of laminitis.
Methodology
- The researchers prepared Polyethylene-glycol (PEG) coated liposomes with the film hydration method. They labelled these liposomes with Technetium-99m, a radioactive tracer, that helped in tracking their progress within the body.
- The study consisted of two groups of horses: six that received a dose of 10g/kg oligofructose to induce laminitis, and a control group of four horses that received water.
- All the horses were intravenously infused with the prepared Technetium-99m liposomes. They were carefully monitored through scintigraphic imaging at intervals of 0, 6, and 12 hours post-infusion.
- Using the imaging, Technetium-99m liposome uptake was measured in specific areas such as the hoof, fetlock, and metacarpus. The aim was to see if the liposomes were accumulating in lamellar tissues.
- At the end of the study, horses were euthanised and tissue samples were collected for further analysis.
Findings
- All horses that received oligofructose developed clinical and histological signs of laminitis.
- For the horses with laminitis, the uptake of Technetium-99m liposomes in the hoof region increased over time, whereas it decreased in the control horses.
- Levels of Technetium-99m liposomes in lamellar tissue from laminitis horses were found to be 3.2-fold higher than in the control group.
- Liposomes were also found in higher levels in the skin, muscle, jejunum, colon, and kidneys of horses with laminitis compared to control horses, suggesting potential systemic inflammation.
Implications
- The results demonstrate that liposomes can effectively accumulate in lamellar tissue during the development of laminitis. This suggests the potential of using liposomes for targeted drug delivery in the treatment of acute laminitis.
- The study also shows that the inflammation associated with laminitis is not limited to the hooves, but can be systemic, a finding that may impact future approaches to laminitis treatment.
Cite This Article
APA
Underwood C, Pollitt CC, Metselaar JM, Laverman P, van Bloois L, van den Hoven JM, Storm G, van Eps AW.
(2015).
Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses.
Vet J, 206(2), 218-225.
https://doi.org/10.1016/j.tvjl.2015.07.013 Publication
Researcher Affiliations
- Australian Equine Laminitis Research Unit, School of Veterinary Science, University of Queensland, Gatton, QLD 4343, Australia. Electronic address: c.underwood1@uq.edu.au.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, University of Queensland, Gatton, QLD 4343, Australia.
- Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
- Radboud University Medical Centre Nijmegen, The Netherlands.
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), University of Utrecht, The Netherlands.
- Department of Pharmacy and Pharmacology, Sloterevaart Hospital, Amsterdam, The Netherlands.
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), University of Utrecht, The Netherlands.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, University of Queensland, Gatton, QLD 4343, Australia.
MeSH Terms
- Animals
- Foot Diseases / diagnostic imaging
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Hoof and Claw / pathology
- Horse Diseases / chemically induced
- Horse Diseases / diagnostic imaging
- Horses
- Inflammation / chemically induced
- Inflammation / diagnostic imaging
- Inflammation / veterinary
- Liposomes / chemistry
- Male
- Oligosaccharides / toxicity
- Polyethylene Glycols / chemistry
- Radiopharmaceuticals / pharmacokinetics
- Technetium Tc 99m Exametazime / pharmacokinetics
Citations
This article has been cited 1 times.- Man F, Gawne PJ, T M de Rosales R. Nuclear imaging of liposomal drug delivery systems: A critical review of radiolabelling methods and applications in nanomedicine. Adv Drug Deliv Rev 2019 Mar 15;143:134-160.
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