Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats
The aim of this work was to study the healing activity of amitriptyline (Amitrip) in rat diabetic wounds. A nanoformula of the drug was prepared as Amitrip-based biodegradable PEG-PLGA self-assembled nanoparticles (Amitrip-NPs) with a mean particle size of 67.4 nm. An in vivo investigation was condu...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/9/1792 |
| _version_ | 1827657815330652160 |
|---|---|
| author | Hani Z. Asfour Nabil A. Alhakamy Osama A. A. Ahmed Usama A. Fahmy Mohamed A. El-moselhy Waleed Y. Rizg Adel F. Alghaith Basma G. Eid Ashraf B. Abdel-Naim |
| author_facet | Hani Z. Asfour Nabil A. Alhakamy Osama A. A. Ahmed Usama A. Fahmy Mohamed A. El-moselhy Waleed Y. Rizg Adel F. Alghaith Basma G. Eid Ashraf B. Abdel-Naim |
| author_sort | Hani Z. Asfour |
| collection | DOAJ |
| description | The aim of this work was to study the healing activity of amitriptyline (Amitrip) in rat diabetic wounds. A nanoformula of the drug was prepared as Amitrip-based biodegradable PEG-PLGA self-assembled nanoparticles (Amitrip-NPs) with a mean particle size of 67.4 nm. An in vivo investigation was conducted to evaluate the wound-healing process of Amitrip-NPs in streptozotocin-induced diabetic rats. Wound contraction was accelerated in rats treated with Amitrip-NPs. Histological examinations confirmed these findings, with expedited remodeling and collagen deposition in the NPs-treated animals. The formula showed anti-inflammatory activities as demonstrated by inhibition of interleukin-6 (IL-6) expression and tumor necrosis factor-α (TNF-α) expression, as well as enhanced expression of interleukin-10 (IL-10). In addition, Amitrip-NPs protected against malondialdehyde (MDA) buildup and superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic exhaustion. The pro-collagen activity of Amitrip-NPs was confirmed by the observed enhancement of hydroxyproline wounded skin content, upregulation of Col 1A1 mRNA expression and immune expression of collagen type IV expression. Further, Amitrip-NPs significantly increased expression transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-B (PDGF-B) and cluster of differentiation 31 (CD31). In conclusion, the developed Amitrip-NPs expedited wound healing in diabetic rats. This involves anti-inflammatory, antioxidant, pro-collagen and angiogenic activities of the prepared NPs. This opens the gate for evaluating the usefulness of other structurally related tricyclic antidepressants in diabetic wounds. |
| first_indexed | 2024-03-09T22:50:13Z |
| format | Article |
| id | doaj.art-4be6534a11e3425a9c4d8e4b5d188cc9 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:50:13Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4be6534a11e3425a9c4d8e4b5d188cc92023-11-23T18:20:38ZengMDPI AGPharmaceutics1999-49232022-08-01149179210.3390/pharmaceutics14091792Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic RatsHani Z. Asfour0Nabil A. Alhakamy1Osama A. A. Ahmed2Usama A. Fahmy3Mohamed A. El-moselhy4Waleed Y. Rizg5Adel F. Alghaith6Basma G. Eid7Ashraf B. Abdel-Naim8Department of Medical Microbiology and Parasitology, Faculty of Medicine, 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 Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Clinical Pharmacy and Pharmacology, Ibn Sina National College for Medical Studies, Jeddah 22413, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, 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 ArabiaThe aim of this work was to study the healing activity of amitriptyline (Amitrip) in rat diabetic wounds. A nanoformula of the drug was prepared as Amitrip-based biodegradable PEG-PLGA self-assembled nanoparticles (Amitrip-NPs) with a mean particle size of 67.4 nm. An in vivo investigation was conducted to evaluate the wound-healing process of Amitrip-NPs in streptozotocin-induced diabetic rats. Wound contraction was accelerated in rats treated with Amitrip-NPs. Histological examinations confirmed these findings, with expedited remodeling and collagen deposition in the NPs-treated animals. The formula showed anti-inflammatory activities as demonstrated by inhibition of interleukin-6 (IL-6) expression and tumor necrosis factor-α (TNF-α) expression, as well as enhanced expression of interleukin-10 (IL-10). In addition, Amitrip-NPs protected against malondialdehyde (MDA) buildup and superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic exhaustion. The pro-collagen activity of Amitrip-NPs was confirmed by the observed enhancement of hydroxyproline wounded skin content, upregulation of Col 1A1 mRNA expression and immune expression of collagen type IV expression. Further, Amitrip-NPs significantly increased expression transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-B (PDGF-B) and cluster of differentiation 31 (CD31). In conclusion, the developed Amitrip-NPs expedited wound healing in diabetic rats. This involves anti-inflammatory, antioxidant, pro-collagen and angiogenic activities of the prepared NPs. This opens the gate for evaluating the usefulness of other structurally related tricyclic antidepressants in diabetic wounds.https://www.mdpi.com/1999-4923/14/9/1792diabetic woundsamitriptylinepolymersPEG-PLGAnanoparticles |
| spellingShingle | Hani Z. Asfour Nabil A. Alhakamy Osama A. A. Ahmed Usama A. Fahmy Mohamed A. El-moselhy Waleed Y. Rizg Adel F. Alghaith Basma G. Eid Ashraf B. Abdel-Naim Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats Pharmaceutics diabetic wounds amitriptyline polymers PEG-PLGA nanoparticles |
| title | Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats |
| title_full | Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats |
| title_fullStr | Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats |
| title_full_unstemmed | Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats |
| title_short | Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats |
| title_sort | amitriptyline based biodegradable peg plga self assembled nanoparticles accelerate cutaneous wound healing in diabetic rats |
| topic | diabetic wounds amitriptyline polymers PEG-PLGA nanoparticles |
| url | https://www.mdpi.com/1999-4923/14/9/1792 |
| work_keys_str_mv | AT hanizasfour amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT nabilaalhakamy amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT osamaaaahmed amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT usamaafahmy amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT mohamedaelmoselhy amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT waleedyrizg amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT adelfalghaith amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT basmageid amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats AT ashrafbabdelnaim amitriptylinebasedbiodegradablepegplgaselfassemblednanoparticlesacceleratecutaneouswoundhealingindiabeticrats |