Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke
Ischemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial dysfunction and increases the risk of stroke. Isoxsuprine is an efficient beta-adrenergic agonist that improves blood flow to the ischemic...
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MDPI AG
2023-08-01
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| Online Access: | https://www.mdpi.com/1999-4923/15/9/2242 |
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| author | Heba A. Abou-Taleb Basmah Nasser Aldosari Randa Mohammed Zaki Obaid Afzal Alaa S. Tulbah Mary Girgis Shahataa Fatma I. Abo El-Ela Heba F. Salem Amr Gamal Fouad |
| author_facet | Heba A. Abou-Taleb Basmah Nasser Aldosari Randa Mohammed Zaki Obaid Afzal Alaa S. Tulbah Mary Girgis Shahataa Fatma I. Abo El-Ela Heba F. Salem Amr Gamal Fouad |
| author_sort | Heba A. Abou-Taleb |
| collection | DOAJ |
| description | Ischemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial dysfunction and increases the risk of stroke. Isoxsuprine is an efficient beta-adrenergic agonist that improves blood flow to the ischemic aria and stops the infarct core from growing. However, low bioavailability, a short biological half-life, and first-pass hepatic metabolism reduce the therapeutic efficacy of oral isoxsuprine. Therefore, the authors focused on developing isoxsuprine-loaded liposomes containing ethanol and propylene glycol (ILEP) formulation as nasal drops for the treatment of ischemic stroke in diabetic patients. Different ILEP formulations were optimized using Design Expert software, and the selected formulation was examined in vivo for its anti-stroke effect using a rat model of diabetes and stroke. The optimized ILEP, composed of 15% propylene glycol, 0.16% cholesterol, 10% ethanol, and 3.29% phospholipid, improved the sustainability, permeation, and targeting of isoxsuprine. Furthermore, the in vivo studies verified the improved neurological behavior and decreased dead shrunken neurons and vascular congestion of the rats treated with the optimized ILEP formulation, demonstrating its anti-stroke activity. In conclusion, our study found that treatment with an optimized ILEP formulation prevented the initiation and severity of stroke, especially in diabetic patients. |
| first_indexed | 2024-03-10T22:16:40Z |
| format | Article |
| id | doaj.art-b3786b7188d5400ab4a7ae25110bcf7b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T22:16:40Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b3786b7188d5400ab4a7ae25110bcf7b2023-11-19T12:26:59ZengMDPI AGPharmaceutics1999-49232023-08-01159224210.3390/pharmaceutics15092242Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated StrokeHeba A. Abou-Taleb0Basmah Nasser Aldosari1Randa Mohammed Zaki2Obaid Afzal3Alaa S. Tulbah4Mary Girgis Shahataa5Fatma I. Abo El-Ela6Heba F. Salem7Amr Gamal Fouad8Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Merit University (MUE), Sohag 1646080, EgyptDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Umm Al Qura University, Makkah 21421, Saudi ArabiaDepartment of Pharmacology, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptIschemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial dysfunction and increases the risk of stroke. Isoxsuprine is an efficient beta-adrenergic agonist that improves blood flow to the ischemic aria and stops the infarct core from growing. However, low bioavailability, a short biological half-life, and first-pass hepatic metabolism reduce the therapeutic efficacy of oral isoxsuprine. Therefore, the authors focused on developing isoxsuprine-loaded liposomes containing ethanol and propylene glycol (ILEP) formulation as nasal drops for the treatment of ischemic stroke in diabetic patients. Different ILEP formulations were optimized using Design Expert software, and the selected formulation was examined in vivo for its anti-stroke effect using a rat model of diabetes and stroke. The optimized ILEP, composed of 15% propylene glycol, 0.16% cholesterol, 10% ethanol, and 3.29% phospholipid, improved the sustainability, permeation, and targeting of isoxsuprine. Furthermore, the in vivo studies verified the improved neurological behavior and decreased dead shrunken neurons and vascular congestion of the rats treated with the optimized ILEP formulation, demonstrating its anti-stroke activity. In conclusion, our study found that treatment with an optimized ILEP formulation prevented the initiation and severity of stroke, especially in diabetic patients.https://www.mdpi.com/1999-4923/15/9/2242strokediabetes mellitusisoxsuprineliposomespropylene glycol |
| spellingShingle | Heba A. Abou-Taleb Basmah Nasser Aldosari Randa Mohammed Zaki Obaid Afzal Alaa S. Tulbah Mary Girgis Shahataa Fatma I. Abo El-Ela Heba F. Salem Amr Gamal Fouad Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke Pharmaceutics stroke diabetes mellitus isoxsuprine liposomes propylene glycol |
| title | Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke |
| title_full | Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke |
| title_fullStr | Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke |
| title_full_unstemmed | Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke |
| title_short | Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke |
| title_sort | formulation and therapeutic evaluation of isoxsuprine loaded nanoparticles against diabetes associated stroke |
| topic | stroke diabetes mellitus isoxsuprine liposomes propylene glycol |
| url | https://www.mdpi.com/1999-4923/15/9/2242 |
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