Drug Design, Development and Therapy (Apr 2023)
Development of Verapamil Hydrochloride-loaded Biopolymer-based Composite Electrospun Nanofibrous Mats: In vivo Evaluation of Enhanced Burn Wound Healing without Scar Formation
Abstract
Hebatallah S Barakat,1 May S Freag,1 Sarah M Gaber,1 Affaf Al Oufy,2,3 Ossama Y Abdallah1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Material & Manufacturing Engineering, Faculty of Engineering, Galala University, Galala, Egypt; 3Department of Textile Engineering, Faculty of Engineering, Alexandria University, Alexandria, EgyptCorrespondence: Hebatallah S Barakat, Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, Messalla Post Office, PO Box 21521, Alexandria, Egypt, Tel +2 01002198334, Email [email protected]: Researchers aim for new heights in wound healing to produce wound dressings with unique features. Natural, synthetic, biodegradable, and biocompatible polymers especially in the nanoscale are being employed to support and provide efficient wound management. Economical and environmentally friendly sustainable wound management alternatives are becoming an urgent issue to meet future needs. Nanofibrous mats possess unique properties for ideal wound healing. They mimic the physical structure of the natural extracellular matrix (ECM), promote hemostasis, and gas permeation. Their interconnected nanoporosity prevents wound dehydration and microbial infiltration.Purpose: To prepare and evaluate a novel verapamil HCl-loaded environmentally friendly composite, with biopolymer-based electrospun nanofibers suitable for application as wound dressings providing adequate wound healing with no scar formation.Methods: Composite nanofibers were prepared by electrospinning of a blend of the natural biocompatible polymers, sodium alginate (SA) or zein (Z) together with polyvinyl alcohol (PVA). Composite nanofibers were characterized in terms of morphology, diameter, drug entrapment efficiency, and release. In vivo study of the therapeutic efficacy of verapamil HCl-loaded nanofibers on a Sprague Dawley rat model with dermal burn wound was investigated in terms of percent wound closure, and presence of scars.Results: Combining PVA with SA or Z improved the electrospinnability and properties of the developed nanofibers. Verapamil HCl-loaded composite nanofibers showed good pharmaceutical attributes favorable for wound healing including, fiber diameter ∼ 150 nm, high entrapment efficiency (∼ 80– 100%) and biphasic controlled drug release for 24 h. In vivo study demonstrated promising potentials for wound healing without scaring.Conclusion: The developed nanofibrous mats combined the beneficial properties of the biopolymers and verapamil HCl to provide an increased functionality by exploiting the unique advantages of nanofibers in wound healing at a small dose proved to be insufficient in case of the conventional dosage form.Graphical Abstract: Keywords: wound dressing, sodium alginate, zein, nanofibers, electrospinning