TY - JOUR
T1 - An in vivo pharmacological study
T2 - Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques
AU - Mooranian, Armin
AU - Zamani, Nassim
AU - Takechi, Ryu
AU - Luna, Giuseppe
AU - Mikov, Momir
AU - Goločorbin-Kon, Svetlana
AU - Elnashar, Magdy
AU - Arfuso, Frank
AU - Al-Salami, Hani
N1 - Funding Information:
This study was funded in part by the Australian Postgraduate Award (APA) and Curtin Research Scholarship (CRS). The authors also acknowledge the Curtin-seeding grant for the support and also acknowledge the use of laboratory equipment, scientific and technical assistance of Microscopy and Microanalysis Facility at Curtin University which has been partially funded by the University, State and Commonwealth Governments. The work is partially supported by the European Union Horizon 2020 MEDLEM research project and innovation program under the Marie Skłodowska-Curie Grant Agreement No 690876. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to acknowledge the Australian Postgraduate Award (APA) and Curtin Research Scholarship (CRS). The authors also acknowledge the Curtin-seeding grant for the support and also acknowledge the use of laboratory equipment, scientific and technical assistance of Microscopy and Microanalysis Facility at Curtin University which has been partially funded by the University, State and Commonwealth Governments. The work is partially supported by the European Union Horizon 2020 MEDLEM research project and innovation program under the Marie Skłodowska-Curie Grant Agreement No 690876.The NIT-1 cells were a generous donation from Professor Grant Morahan at the University of Western Australia.
Publisher Copyright:
© 2019 Mooranian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/4
Y1 - 2019/4
N2 - Type 2 diabetes (T2D) is characterised by β-cell damage and hyperglycaemia. The lipophilic drug, probucol, has shown significant β-cell protective and potential antidiabetic effects, which were enhanced by hydrophilic bile acid incorporation using taurocholic acid and chenodeoxycholic acid. However, probucol has severe cardiotoxicity and a variable absorption profile, which limit its potential applications in T2D. Accordingly, this study aimed to design multiple formulations to optimise probucol oral delivery in T2D and test their effects on probucol absorption and accumulation in the heart. Adult male mice were given a high fat diet (HFD), and a week later, injected with a single dose of alloxan to accelerate T2D development, and once diabetes confirmed, divided into three groups (six to seven mice each). The groups were gavaged a daily dose of probucol powder, probucol microcapsules, or probucol-bile acid microcapsules for three months, and euthanized; and blood, tissues, and feces collected for blood glucose and probucol concentration analyses. Probucol concentrations in plasma were similar among all the groups. Groups given probucol microcapsules and probucol-bile acid microcapsules showed significant reduction in probucol accumulation in the heart compared with the group given probucol powder (p
AB - Type 2 diabetes (T2D) is characterised by β-cell damage and hyperglycaemia. The lipophilic drug, probucol, has shown significant β-cell protective and potential antidiabetic effects, which were enhanced by hydrophilic bile acid incorporation using taurocholic acid and chenodeoxycholic acid. However, probucol has severe cardiotoxicity and a variable absorption profile, which limit its potential applications in T2D. Accordingly, this study aimed to design multiple formulations to optimise probucol oral delivery in T2D and test their effects on probucol absorption and accumulation in the heart. Adult male mice were given a high fat diet (HFD), and a week later, injected with a single dose of alloxan to accelerate T2D development, and once diabetes confirmed, divided into three groups (six to seven mice each). The groups were gavaged a daily dose of probucol powder, probucol microcapsules, or probucol-bile acid microcapsules for three months, and euthanized; and blood, tissues, and feces collected for blood glucose and probucol concentration analyses. Probucol concentrations in plasma were similar among all the groups. Groups given probucol microcapsules and probucol-bile acid microcapsules showed significant reduction in probucol accumulation in the heart compared with the group given probucol powder (p
UR - http://www.scopus.com/inward/record.url?scp=85064000896&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0214984
DO - 10.1371/journal.pone.0214984
M3 - Article
C2 - 30947243
AN - SCOPUS:85064000896
SN - 1932-6203
VL - 14
JO - PLoS One
JF - PLoS One
IS - 4
M1 - e0214984
ER -
