Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds

Diabetic hyperglycemia delays wound healing, leading to serious consequences. Topical antibiotics can reduce the risk of a wound infection during healing; nevertheless, the microbial fight against antibiotics brings about public health challenges. Anti-microbial peptides (AMPs) belong to a novel cla...

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Main Authors: Abdullah A. Alamoudi, Awaad S. Alharbi, Ashraf B. Abdel-Naim, Shaimaa M. Badr-Eldin, Zuhier A. Awan, Solomon Z. Okbazghi, Osama A. A. Ahmed, Nabil A. Alhakamy, Usama A. Fahmy, Ahmed Esmat
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/12/7/1096
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author Abdullah A. Alamoudi
Awaad S. Alharbi
Ashraf B. Abdel-Naim
Shaimaa M. Badr-Eldin
Zuhier A. Awan
Solomon Z. Okbazghi
Osama A. A. Ahmed
Nabil A. Alhakamy
Usama A. Fahmy
Ahmed Esmat
author_facet Abdullah A. Alamoudi
Awaad S. Alharbi
Ashraf B. Abdel-Naim
Shaimaa M. Badr-Eldin
Zuhier A. Awan
Solomon Z. Okbazghi
Osama A. A. Ahmed
Nabil A. Alhakamy
Usama A. Fahmy
Ahmed Esmat
author_sort Abdullah A. Alamoudi
collection DOAJ
description Diabetic hyperglycemia delays wound healing, leading to serious consequences. Topical antibiotics can reduce the risk of a wound infection during healing; nevertheless, the microbial fight against antibiotics brings about public health challenges. Anti-microbial peptides (AMPs) belong to a novel class of drug that is used to prevent and treat systemic and topical infections. The aim of the current work was to achieve better wound healing in diabetic rats by conjugating the anti-microbial peptide “apamin” (APA) with the broad-spectrum antibiotic “ceftriaxone” (CTX) to form a nanocomplex. The CTX–APA nanoconjugate formulation was optimized using a Box–Behnken design. The optimized CTX–APA nanoconjugate formulation was evaluated for its size and zeta potential, and was then examined using transmission electron microscopy (TEM). The CTX–APA nanoconjugate was loaded onto a hydroxypropyl methylcellulose (2% <i>w</i>/<i>v</i>)-based hydrogel. It was observed that the application of the CTX–APA nanocomplex on the wounded skin of diabetic rats accelerated the regeneration of the epithelium, granulation tissue formation, epidermal proliferation, and keratinization. The nanocomplex was capable of significantly reducing the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), while increasing the expression of transforming growth factor beta-1 (TGF-β1) as well as the angiogenic markers: hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Conclusively, the application of an ion-paired CTX–APA nanocomplex enhances wound healing in diabetic rats.
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spelling doaj.art-c9e09026a9644b20aba4080629dd15d72023-11-30T21:18:37ZengMDPI AGLife2075-17292022-07-01127109610.3390/life12071096Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic WoundsAbdullah A. Alamoudi0Awaad S. Alharbi1Ashraf B. Abdel-Naim2Shaimaa M. Badr-Eldin3Zuhier A. Awan4Solomon Z. Okbazghi5Osama A. A. Ahmed6Nabil A. Alhakamy7Usama A. Fahmy8Ahmed Esmat9Department 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 Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaGlobal Analytical and Pharmaceutical Development, Alexion Pharmaceuticals, New Haven, CT 06510, USADepartment 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 Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDiabetic hyperglycemia delays wound healing, leading to serious consequences. Topical antibiotics can reduce the risk of a wound infection during healing; nevertheless, the microbial fight against antibiotics brings about public health challenges. Anti-microbial peptides (AMPs) belong to a novel class of drug that is used to prevent and treat systemic and topical infections. The aim of the current work was to achieve better wound healing in diabetic rats by conjugating the anti-microbial peptide “apamin” (APA) with the broad-spectrum antibiotic “ceftriaxone” (CTX) to form a nanocomplex. The CTX–APA nanoconjugate formulation was optimized using a Box–Behnken design. The optimized CTX–APA nanoconjugate formulation was evaluated for its size and zeta potential, and was then examined using transmission electron microscopy (TEM). The CTX–APA nanoconjugate was loaded onto a hydroxypropyl methylcellulose (2% <i>w</i>/<i>v</i>)-based hydrogel. It was observed that the application of the CTX–APA nanocomplex on the wounded skin of diabetic rats accelerated the regeneration of the epithelium, granulation tissue formation, epidermal proliferation, and keratinization. The nanocomplex was capable of significantly reducing the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), while increasing the expression of transforming growth factor beta-1 (TGF-β1) as well as the angiogenic markers: hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Conclusively, the application of an ion-paired CTX–APA nanocomplex enhances wound healing in diabetic rats.https://www.mdpi.com/2075-1729/12/7/1096anti-microbial peptidesceftriaxoneapaminhydrogeldiabetic woundsoptimization
spellingShingle Abdullah A. Alamoudi
Awaad S. Alharbi
Ashraf B. Abdel-Naim
Shaimaa M. Badr-Eldin
Zuhier A. Awan
Solomon Z. Okbazghi
Osama A. A. Ahmed
Nabil A. Alhakamy
Usama A. Fahmy
Ahmed Esmat
Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds
Life
anti-microbial peptides
ceftriaxone
apamin
hydrogel
diabetic wounds
optimization
title Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds
title_full Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds
title_fullStr Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds
title_full_unstemmed Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds
title_short Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds
title_sort novel nanoconjugate of apamin and ceftriaxone for management of diabetic wounds
topic anti-microbial peptides
ceftriaxone
apamin
hydrogel
diabetic wounds
optimization
url https://www.mdpi.com/2075-1729/12/7/1096
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