Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment

Impaired diabetic wound healing is a major concern for health care professionals worldwide, imposing an intense financial burden and reducing the quality of life of patients. A dysregulation of this process can be responsible for the development of intractable ulcers and the formation of excessive s...

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Main Authors: Nabil A. Alhakamy, Giuseppe Caruso, Anna Privitera, Osama A. A. Ahmed, Usama A. Fahmy, Shadab Md, Gamal A. Mohamed, Sabrin R. M. Ibrahim, Basma G. Eid, Ashraf B. Abdel-Naim, Filippo Caraci
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/14/6/1133
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author Nabil A. Alhakamy
Giuseppe Caruso
Anna Privitera
Osama A. A. Ahmed
Usama A. Fahmy
Shadab Md
Gamal A. Mohamed
Sabrin R. M. Ibrahim
Basma G. Eid
Ashraf B. Abdel-Naim
Filippo Caraci
author_facet Nabil A. Alhakamy
Giuseppe Caruso
Anna Privitera
Osama A. A. Ahmed
Usama A. Fahmy
Shadab Md
Gamal A. Mohamed
Sabrin R. M. Ibrahim
Basma G. Eid
Ashraf B. Abdel-Naim
Filippo Caraci
author_sort Nabil A. Alhakamy
collection DOAJ
description Impaired diabetic wound healing is a major concern for health care professionals worldwide, imposing an intense financial burden and reducing the quality of life of patients. A dysregulation of this process can be responsible for the development of intractable ulcers and the formation of excessive scars. Therefore, the identification of novel pharmacological strategies able to promote wound healing and restore the mechanical integrity of injured tissue becomes essential. In the present study, fluoxetine ecofriendly nanoemulsion (FLX-EFNE) was prepared and its potential efficacy in enhancing wound healing was tested in diabetic rats. The Box–Behnken response surface design was used to select the optimized formulation that was prepared by the high-shear homogenization-based technique. A Zetasizer was used for the characterization of the optimized formulation, providing a FLX-EFNE with a globule size of 199 nm. For the in vivo study, a wound was induced by surgical methods, and diabetic rats (streptozotocin-induced) were divided into five groups: untreated control, vehicle-treated, FLX, FLX-EFNE, and positive control receiving a commercially available formula. The treatment continued from the day of wound induction to day 21. Then, the animals were sacrificed and skin tissues were collected at the site of wounding and used for biochemical, histopathological, immunohistochemical, and mRNA expression assessments. In the FLX-EFNE treated group, the rate of wound contraction and signs of healing were significantly higher compared to all other groups. In addition, angiogenesis, proliferation, and collagen deposition were enhanced, while oxidative stress and inflammation decreased. The present data highlight the enhanced wound healing activity of the optimized FLX-EFNE formulation.
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spelling doaj.art-31c0dbb1ebac47aea318a8b45023de132023-11-23T18:28:45ZengMDPI AGPharmaceutics1999-49232022-05-01146113310.3390/pharmaceutics14061133Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy AssessmentNabil A. Alhakamy0Giuseppe Caruso1Anna Privitera2Osama A. A. Ahmed3Usama A. Fahmy4Shadab Md5Gamal A. Mohamed6Sabrin R. M. Ibrahim7Basma G. Eid8Ashraf B. Abdel-Naim9Filippo Caraci10Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Drug and Health Sciences, University of Catania, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, 95125 Catania, ItalyDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaPreparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Drug and Health Sciences, University of Catania, 95125 Catania, ItalyImpaired diabetic wound healing is a major concern for health care professionals worldwide, imposing an intense financial burden and reducing the quality of life of patients. A dysregulation of this process can be responsible for the development of intractable ulcers and the formation of excessive scars. Therefore, the identification of novel pharmacological strategies able to promote wound healing and restore the mechanical integrity of injured tissue becomes essential. In the present study, fluoxetine ecofriendly nanoemulsion (FLX-EFNE) was prepared and its potential efficacy in enhancing wound healing was tested in diabetic rats. The Box–Behnken response surface design was used to select the optimized formulation that was prepared by the high-shear homogenization-based technique. A Zetasizer was used for the characterization of the optimized formulation, providing a FLX-EFNE with a globule size of 199 nm. For the in vivo study, a wound was induced by surgical methods, and diabetic rats (streptozotocin-induced) were divided into five groups: untreated control, vehicle-treated, FLX, FLX-EFNE, and positive control receiving a commercially available formula. The treatment continued from the day of wound induction to day 21. Then, the animals were sacrificed and skin tissues were collected at the site of wounding and used for biochemical, histopathological, immunohistochemical, and mRNA expression assessments. In the FLX-EFNE treated group, the rate of wound contraction and signs of healing were significantly higher compared to all other groups. In addition, angiogenesis, proliferation, and collagen deposition were enhanced, while oxidative stress and inflammation decreased. The present data highlight the enhanced wound healing activity of the optimized FLX-EFNE formulation.https://www.mdpi.com/1999-4923/14/6/1133diabetic woundfluoxetineecofriendlynanoemulsionoxidative stressinflammation
spellingShingle Nabil A. Alhakamy
Giuseppe Caruso
Anna Privitera
Osama A. A. Ahmed
Usama A. Fahmy
Shadab Md
Gamal A. Mohamed
Sabrin R. M. Ibrahim
Basma G. Eid
Ashraf B. Abdel-Naim
Filippo Caraci
Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment
Pharmaceutics
diabetic wound
fluoxetine
ecofriendly
nanoemulsion
oxidative stress
inflammation
title Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment
title_full Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment
title_fullStr Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment
title_full_unstemmed Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment
title_short Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment
title_sort fluoxetine ecofriendly nanoemulsion enhances wound healing in diabetic rats in vivo efficacy assessment
topic diabetic wound
fluoxetine
ecofriendly
nanoemulsion
oxidative stress
inflammation
url https://www.mdpi.com/1999-4923/14/6/1133
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