title: Single-Dose Electrospun Nanoparticles-in-Nanofibers Wound Dressings with Enhanced Epithelialization, Collagen Deposition, and Granulation Properties.
abstract: Phenytoin (Ph), an antiepileptic drug, was reported to exhibit high wound healing activity. However, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop new single-dose electrospun nanoparticles-in-nanofibers (NPs-in-NFs) wound dressings that allow a well-controlled release of Ph. These NPs-in-NFs systems are based on enhanced chitosan (CS)/poly(ethylene oxide) (PEO) electrospun nanofibers (NFs) incorporating optimized Ph-loaded nanocarriers. First, a study was conducted to investigate Ph loading efficiency into polymeric nanocarriers of different types; pluronic nanomicelles and poly(lactic-co-glycolic) acids nanoparticles (PLGA NPs). The drug release profile from the nanocarriers was further optimized via lecithin coating. Second, different electrospinning parameters were manipulated to fabricate beads-free homogeneous NFs with optimized polymer ratios. Plain and Ph-loaded nanocarriers were characterized using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Both entrapment efficiency of Ph (EE%) and its release profile in phosphate buffer saline (PBS; pH 5.5), simulating the wound environment, were studied. Biodegradability, swelling, vapor permeability, and porosity of the developed Ph-loaded NPs-in-NFs wound dressings were investigated. Morphology of the NPs-in-NFs was also studied using SEM and confocal laser microscopy (CLSM). Besides, the release profiles of Ph from the optimized NPs-in-NFs were assessed. The newly developed wound dressings were evaluated in vitro for their cytotoxicity using human fibroblasts and in vivo using a wound healing mice model. Nanocarriers with particle size ranging from 100 to 180 nm were successfully prepared. All nanocarriers attained a high drug entrapment efficiency exceeding 94% and showed promising sustained release profiles compared to free Ph. Results also demonstrated that NFs incorporating the optimized lecithin-coated Ph-loaded PLGA NPs could be the most promising candidate for efficient wound healing. These NPs-in-NFs systems conferred a well-controlled and sustained release of Ph over 9 days. Moreover, they showed the best re-epithelization and healing quality during the in vivo study with minimal inflammatory and necrotic cells formation.
authors.affiliation: Nanomaterials Lab, Center of Material Science (CMS), Zewail City of Science and Technology , 6th of October, Giza 12588, Egypt.
authors.forename: Isra H
authors.initials: IH
authors.lastname: Ali
authors.affiliation: Nanomaterials Lab, Center of Material Science (CMS), Zewail City of Science and Technology , 6th of October, Giza 12588, Egypt.|Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology (MUST) , 6th of October, Giza 12566, Egypt.
authors.forename: Islam A
authors.initials: IA
authors.lastname: Khalil
authors.affiliation: Nanomaterials Lab, Center of Material Science (CMS), Zewail City of Science and Technology , 6th of October, Giza 12588, Egypt.
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Sherbiny
mesh_terms: D000818:Animals; D001458:Bandages; D003094:Collagen / Q000378:metabolism*; D065546:Drug Liberation; D006801:Humans; D057139:Nanofibers / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D062326:Re-Epithelialization
chemical_list: D003094:Collagen
keywords: chitosan; electrospun; nanofibers; phenytoin; single-dose; wound healing