International Journal of Nanomedicine (Oct 2023)
Carvacrol-Loaded Phytosomes for Enhanced Wound Healing: Molecular Docking, Formulation, DoE-Aided Optimization, and in vitro/in vivo Evaluation
Abstract
Ahmed Mowafy Tafish,1,2 Mohamed El-Sherbiny,3,4 Ahmed A Al‐Karmalawy,5,6 Osama Abd El-Azeem Soliman,1 Noha Mohamed Saleh1 1Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Horus University, New Damietta, 34518, Egypt; 3Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia; 4Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University, New Damietta, 34518, Egypt; 6Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, 12566, EgyptCorrespondence: Noha Mohamed Saleh, Associate Professor of Pharmaceutics, Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt, Tel +2 01064536677, Fax +2 050 2247496, Email [email protected]: Despite recent advances in wound healing products, phytochemicals have been considered promising and attractive alternatives. Carvacrol (CAR), a natural phenolic compound, has been reported to be effective in wound healing.Purpose: This work endeavored to develop novel CAR-loaded phytosomes for the enhancement of the wound healing process.Methods: Molecular docking was performed to compare the affinities of the different types of phospholipids to CAR. Phytosomes were prepared by three methods (thin-film hydration, cosolvency, and salting out) using Lipoid S100 and Phospholipon 90H with three levels of saturation percent (0%, 50%, and 100%), and three levels of phospholipid molar percent (66.67%, 75%, and 80%). The optimization was performed using Design Expert where particle size, polydispersity index, and zeta potential were chosen as dependent variables. The optimized formula (F1) was further investigated regarding entrapment efficiency, TEM, 1H-NMR, FT-IR, DSC, X-RD, in vitro release, ex vivo permeation, and stability. Furthermore, it was incorporated into a hydrogel formulation, and an in vivo study was conducted to investigate the wound-healing properties of F1.Results: F1 was chosen as the optimized formula prepared via the thin-film hydration method with a saturation percent and a phospholipid molar percent of zero and 66.67, respectively. TEM revealed the spherical shape of phytosomal vesicles with uniform size, while the results of 1H-NMR, FT-IR, DSC, and X-RD confirmed the formation of the phytosomal complex. F1 demonstrated a higher in vitro release and a slower permeation than free CAR. The wound area of F1-treated animals showed a marked reduction associated with a high degree of collagen fiber deposition and enhanced cellular proliferation.Conclusion: F1 can be considered as a promising remedy for the enhancement of wound healing and hence it would be hoped to undergo further investigation.Graphical Abstract: Keywords: carvacrol, phospholipids, docking, phytosome, release, topical, wound healing
