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.
The management of serious corneal infections often requires complex therapeutic regimens involving prolonged and high-frequency application of antibiotics that provide many challenges to patients, and impact compliance with the therapeutic...
Advanced
bone healing approaches included a wide range of biomaterials
that mainly mimic the composition, structure, and properties of bone
extracellular matrix with osteogenic activity. The present study aimed
to develop a sandwich-like structure of electrospun nanofibers (NFs)
based on polycaprolactone (PCL) and chitosan/polyethylene oxide (CS/PEO)
composite to stimulate bone fracture healing. The morphology of the
fabricated scaffolds was examined using scanning electron microscopy
(SEM). Apatite deposition was evaluated using simulated body fluid
(SBF). The physicochemical and mechanical properties of samples were
analyzed by Fourier transform infrared, differential scanning calorimetry
(DSC), thermogravimetric analysis (TGA), and universal testing machine.
SEM images exhibited a porous three-dimensional structure with NF
diameters of 514−4745 nm and 68−786 nm for PCL NFs layer
and the sandwich-like NFs scaffolds, respectively. Deposition of apatite
crystal on scaffolds started at week 2 followed by heavy deposition
at week 8. This was confirmed by measuring the consumption of calcium
and phosphorous ions from SBF. Thermal stability of scaffolds was
confirmed using DSC and TGA. Moreover, the PCL NF layer in the middle
of the developed sandwich structure reinforced the scaffolds with
bear load up to 12.224 ± 1.12 MPa and Young’s modulus
of 17.53 ± 3.24 MPa. The scaffolds’ porous structure enhanced
both cell propagation and proliferation. Besides, the presence of
CS in the outer NF layers of the scaffolds increased the hydrophilicity,
as evidenced by the reduction of contact angle from 116.6 to 57.6°,
which is essential for cell attachment. Cell viability study on mesenchymal
stem cells proved the cytocompatibility of the fabricated scaffolds.
Finally, in vivo mandibular bone defect rabbit model was used to confirm
the regeneration of a new healthy bone within 28 days. In conclusion,
the developed scaffolds could be a promising solution to stimulate
bone regeneration.
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