An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques
© 2019 Mooranian et al. 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 che...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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PUBLIC LIBRARY SCIENCE
2019
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| Online Access: | http://hdl.handle.net/20.500.11937/82373 |
| _version_ | 1848764495490449408 |
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| author | Mooranian, Armin Zamani, Nassim Takechi, Ryu Luna, Giuseppe Mikov, M. Goločorbin-Kon, S. Elnashar, Magdy Arfuso, Frank Al-Salami, Hani |
| author_facet | Mooranian, Armin Zamani, Nassim Takechi, Ryu Luna, Giuseppe Mikov, M. Goločorbin-Kon, S. Elnashar, Magdy Arfuso, Frank Al-Salami, Hani |
| author_sort | Mooranian, Armin |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2019 Mooranian et al.
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<0.05). Probucol microencapsulation with or without bile acids reduced its accumulation in heart tissues, without changing plasma concentrations, which may be beneficial in reducing its cardiotoxicity and optimise its potential applications in T2D. |
| first_indexed | 2025-11-14T11:20:16Z |
| format | Journal Article |
| id | curtin-20.500.11937-82373 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:20:16Z |
| publishDate | 2019 |
| publisher | PUBLIC LIBRARY SCIENCE |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-823732021-02-02T04:09:38Z An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques Mooranian, Armin Zamani, Nassim Takechi, Ryu Luna, Giuseppe Mikov, M. Goločorbin-Kon, S. Elnashar, Magdy Arfuso, Frank Al-Salami, Hani Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics POTENTIAL ANTIDIABETIC DRUG BILE-ACID INSULIN SENSITIVITY DELIVERY MICROENCAPSULATION FORMULATION MICROCAPSULES MUSCLES STRESS © 2019 Mooranian et al. 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<0.05). Probucol microencapsulation with or without bile acids reduced its accumulation in heart tissues, without changing plasma concentrations, which may be beneficial in reducing its cardiotoxicity and optimise its potential applications in T2D. 2019 Journal Article http://hdl.handle.net/20.500.11937/82373 10.1371/journal.pone.0214984 English http://creativecommons.org/licenses/by/4.0/ PUBLIC LIBRARY SCIENCE fulltext |
| spellingShingle | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics POTENTIAL ANTIDIABETIC DRUG BILE-ACID INSULIN SENSITIVITY DELIVERY MICROENCAPSULATION FORMULATION MICROCAPSULES MUSCLES STRESS Mooranian, Armin Zamani, Nassim Takechi, Ryu Luna, Giuseppe Mikov, M. Goločorbin-Kon, S. Elnashar, Magdy Arfuso, Frank Al-Salami, Hani An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques |
| title | An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques |
| title_full | An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques |
| title_fullStr | An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques |
| title_full_unstemmed | An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques |
| title_short | An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques |
| title_sort | in vivo pharmacological study: variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques |
| topic | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics POTENTIAL ANTIDIABETIC DRUG BILE-ACID INSULIN SENSITIVITY DELIVERY MICROENCAPSULATION FORMULATION MICROCAPSULES MUSCLES STRESS |
| url | http://hdl.handle.net/20.500.11937/82373 |