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Eid BG, Alhakamy NA, Fahmy UA, et al. Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-β1. Pharmacol Res. 2021;175:105993doi: 10.1016/j.phrs.2021.105993.
Eid, B. G., Alhakamy, N. A., Fahmy, U. A., Ahmed, O. A. A., Md, S., Abdel-Naim, A. B., Caruso, G., & Caraci, F. (2021). Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-β1. Pharmacological research, 175105993. https://doi.org/10.1016/j.phrs.2021.105993
Eid, Basma G, et al. "Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-β1." Pharmacological research vol. 175 (2021): 105993. doi: https://doi.org/10.1016/j.phrs.2021.105993
Eid BG, Alhakamy NA, Fahmy UA, Ahmed OAA, Md S, Abdel-Naim AB, Caruso G, Caraci F. Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-β1. Pharmacol Res. 2021 Nov 19;175:105993. doi: 10.1016/j.phrs.2021.105993. Epub 2021 Nov 19. PMID: 34801680.
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Pharmacol Res. 2021 Nov 19;175:105993. doi: 10.1016/j.phrs.2021.105993. Epub 2021 Nov 19.

Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-β1.

Pharmacological research

Basma G Eid, Nabil A Alhakamy, Usama A Fahmy, Osama A A Ahmed, Shadab Md, Ashraf B Abdel-Naim, Giuseppe Caruso, Filippo Caraci

Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  2. Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Scientific chair "Mohamed Saeed Tamer Chair for Pharmaceutical industries", King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  3. Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  4. Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy. Electronic address: [email protected].
  5. Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy; Oasi Research Institute-IRCCS, 94018 Troina, Italy. Electronic address: [email protected].

PMID: 34801680 DOI: 10.1016/j.phrs.2021.105993

Abstract

A dysregulation of the wound healing process can lead to the development of various intractable ulcers or excessive scar formation. Therefore it is essential to identify novel pharmacological strategies to promote wound healing and restore the mechanical integrity of injured tissue. The goal of the present study was to formulate a nano-complex containing melittin (MEL) and diclofenac (DCL) with the aim to evaluate their synergism and preclinical efficacy in an in vivo model of acute wound. After its preparation and characterization, the therapeutic potential of the combined nano-complexes was evaluated. MEL-DCL nano-complexes exhibited better regenerated epithelium, keratinization, epidermal proliferation, and granulation tissue formation, which in turn showed better wound healing activity compared to MEL, DCL, or positive control. The nano-complexes also showed significantly enhanced antioxidant activity. Treatment of wounded skin with MEL-DCL nano-complexes showed significant reduction of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) pro-inflammatory markers that was paralleled by a substantial increase in mRNA expression levels of collagen, type I, alpha 1 (Col1A1) and collagen, type IV, alpha 1 (Col4A1), and hydroxyproline content as compared to individual drugs. Additionally, MEL-DCL nano-complexes were able to significantly increase hypoxia-inducible factor 1-alpha (HIF-1α) and transforming growth factor beta 1 (TGF-β1) proteins expression compared to single drugs or negative control group. SB431542, a selective inhibitor of type-1 TGF-β receptor, significantly prevented in our in vitro assay the wound healing process induced by the MEL-DCL nano-complexes, suggesting a key role of TGF-β1 in the wound closure. In conclusion, the nano-complex of MEL-DCL represents a novel pharmacological tool that can be topically applied to improve wound healing.

Copyright © 2021. Published by Elsevier Ltd.

Keywords: Diclofenac; Ion pairing; Mellitin; Nano-complex; TGF-β1; Wound healing

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