Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses

Claire Underwood, Christopher C. Pollitt, Josbert Maarten Metselaar, Peter Laverman, Louis van Bloois, Jolanda M. van den Hoven, Gerrit Storm, Andrew W. van Eps

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

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 99mTc-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 99mTc-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 99mTc-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.
Original languageUndefined
Pages (from-to)218-225
JournalVetinerary journal
Volume206
Issue number2
DOIs
Publication statusPublished - 2015

Keywords

  • METIS-315192
  • IR-99921

Cite this

Underwood, C., Pollitt, C. C., Metselaar, J. M., Laverman, P., van Bloois, L., van den Hoven, J. M., ... van Eps, A. W. (2015). Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses. Vetinerary journal, 206(2), 218-225. https://doi.org/10.1016/j.tvjl.2015.07.013
Underwood, Claire ; Pollitt, Christopher C. ; Metselaar, Josbert Maarten ; Laverman, Peter ; van Bloois, Louis ; van den Hoven, Jolanda M. ; Storm, Gerrit ; van Eps, Andrew W. / Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses. In: Vetinerary journal. 2015 ; Vol. 206, No. 2. pp. 218-225.
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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 99mTc-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 99mTc-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 99mTc-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.",
keywords = "METIS-315192, IR-99921",
author = "Claire Underwood and Pollitt, {Christopher C.} and Metselaar, {Josbert Maarten} and Peter Laverman and {van Bloois}, Louis and {van den Hoven}, {Jolanda M.} and Gerrit Storm and {van Eps}, {Andrew W.}",
year = "2015",
doi = "10.1016/j.tvjl.2015.07.013",
language = "Undefined",
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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' Vetinerary journal, vol. 206, no. 2, pp. 218-225. https://doi.org/10.1016/j.tvjl.2015.07.013

Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses. / Underwood, Claire; Pollitt, Christopher C.; Metselaar, Josbert Maarten; Laverman, Peter; van Bloois, Louis; van den Hoven, Jolanda M.; Storm, Gerrit; van Eps, Andrew W.

In: Vetinerary journal, Vol. 206, No. 2, 2015, p. 218-225.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses

AU - Underwood, Claire

AU - Pollitt, Christopher C.

AU - Metselaar, Josbert Maarten

AU - Laverman, Peter

AU - van Bloois, Louis

AU - van den Hoven, Jolanda M.

AU - Storm, Gerrit

AU - van Eps, Andrew W.

PY - 2015

Y1 - 2015

N2 - 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 99mTc-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 99mTc-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 99mTc-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.

AB - 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 99mTc-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 99mTc-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 99mTc-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.

KW - METIS-315192

KW - IR-99921

U2 - 10.1016/j.tvjl.2015.07.013

DO - 10.1016/j.tvjl.2015.07.013

M3 - Article

VL - 206

SP - 218

EP - 225

JO - Vetinerary journal

JF - Vetinerary journal

SN - 1090-0233

IS - 2

ER -

Underwood C, Pollitt CC, Metselaar JM, Laverman P, van Bloois L, van den Hoven JM et al. Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses. Vetinerary journal. 2015;206(2):218-225. https://doi.org/10.1016/j.tvjl.2015.07.013