Development of Cephradine-Loaded Gelatin/Polyvinyl Alcohol Electrospun Nanofibers for Effective Diabetic Wound Healing: In-Vitro and In-Vivo Assessments

Abstract

Diabetic wound infections caused by conventional antibiotic-resistant Staphylococcus aureus strains are fast emerging, leading to life-threatening situations (e.g., high costs, morbidity, and mortality) associated with delayed healing and chronic inflammation. Electrospinning is one of the most widely used techniques for the fabrication of nanofibers (NFs), induced by a high voltage applied to a drug-loaded polymer solution. Particular attention is given to electrospun NFs for pharmaceutical applications (e.g., original drug delivery systems) and tissue regeneration (e.g., as tissue scaffolds). However, there is a paucity of reports related to their application in diabetic wound infections. Therefore, we prepared eco-friendly, biodegradable, low-immunogenic, and biocompatible gelatin (GEL)/polyvinyl alcohol (PVA) electrospun NFs (BNFs), in which we loaded the broad-spectrum antibiotic cephradine (Ceph). The resulting drug-loaded NFs (LNFs) were characterized physically using ultraviolet-visible (UV-Vis) spectrophotometry (for drug loading capacity (LC), drug encapsulation efficiency (EE), and drug release kinetics determination), thermogravimetric analysis (TGA) (for thermostability evaluation), scanning electron microscopy (SEM) (for surface morphology analysis), and Fourier-transform infrared spectroscopy (FTIR) (for functional group identification). LNFs were further characterized biologically by in-vitro assessment of their potency against S. aureus clinical strains (N = 16) using the Kirby–Bauer test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, by ex-vivo assessment to evaluate their cytotoxicity against primary human epidermal keratinocytes using MTT assay, and by in-vivo assessment to estimate their diabetic chronic wound-healing efficiency using NcZ10 diabetic/obese mice (N = 18). Thin and uniform NFs with a smooth surface and standard size (<400 nm) were observed by SEM at the optimized 5:5 (GEL:PVA) volumetric ratio. FTIR analyses confirmed the drug loading into BNFs. Compared to free Ceph, LNFs were significantly more thermostable and exhibited sustained/controlled Ceph release. LNFs also exerted a significantly stronger antibacterial activity both in-vitro and in-vivo. LNFs were significantly safer and more efficient for bacterial clearance-induced faster chronic wound healing. LNF-based therapy could be employed as a valuable dressing material to heal S. aureus-induced chronic wounds in diabetic subjects.

Breast Cancer Inhibition by Biosynthesized Titanium Dioxide Nanoparticles Is Comparable to Free Doxorubicin but Appeared Safer in BALB/c Mice

“…The data were expressed as mean ± standard deviation (SD). Statistical analyses of tumor size and weight in the animal studies were conducted using the Student's t-test and Origin Pro8 software [57]. * P-values < 0.05 were considered significant while # P-values > 0.05 were considered insignificant.…”

“…Twenty-one days later, at the end of experiment, all the mice were simultaneously sacrificed by cervical dislocation [57]. Tumors from each group were subsequently excised, weighed, and photographed.…”

Superfast Synthesis of Stabilized Silver Nanoparticles Using Aqueous Allium sativum (Garlic) Extract and Isoniazid Hydrazide Conjugates: Molecular Docking and In-Vitro Characterizations

“…To assess the kinetic modeling, the dissolution data of the best formulation (F13) in pH conditions (pH 5.7 and pH 7.2) were incorporated to various mathematical models ( Table 5 ), like zero order, first order, Higuchi, Korsmeyer-Peppas models to establish the kinetics of drug release [ 46 ].…”

In vitro and in vivo advancement of multifunctional electrospun nanofiber scaffolds in wound healing applications: Innovative nanofiber designs, stem cell approaches, and future perspectives

“…Wound dressings consisting of electrospun nanofibers mesh made of natural, semi‐synthetic, and fully synthetic polymers have been used. Gelatin, a natural polymer, is widely used in combination with other synthetic biodegradable polymers such as PCL, 113,123,131 Poly(lactide‐co‐ε‐caprolactone), 122 PLA, 126 PVA, 147 and cellulose acetate 117 to create bioinspired nanofibers for in vitro as well as in vivo wound healing applications. Incorporation of gelatin in nanofibers promotes fibroblasts and keratinocytes attachment, migration, and proliferation, as well as the essential ECM components secretion such as collagens in vitro and speeds up wound healing in vivo due to its fascinating cell‐favorable biological features such as biocompatibility, biodegradability, and bioactivity.…”