Preparation and Characterization of Silver Sulfadiazine–Loaded Polyvinyl Alcohol Hydrogels as an Antibacterial Wound Dressing

Abstract

In this study, we prepared a series of silver sulfadiazine (AgSD)–loaded polyvinyl alcohol (PVA) hydrogels via electron beam (e-beam) irradiation. Our objective was to explore the influence of e-beam irradiation on the chemical structure and crystallinity of AgSD and the antibacterial properties of AgSD/PVA hydrogels. Prior to irradiation, we mixed AgSD in PVA solution in 2 forms, either suspended in water (WS) or dissolved in ammonia solution (AS). We noted that nano silver was released from AgSD/PVA-AS hydrogels immersed in deionized water, while it would not happen in AgSD/PVA-WS hydrogels. Both kinds of AgSD/PVA hydrogels exhibited good antibacterial activities against gram-negative Escherichia coli and gram-positive Staphylococcus aureus. And their antibacterial activity was not obviously affected by different dosages of e-beam irradiation. Moreover, the antibacterial activity of the AgSD/PVA-WS hydrogels was stronger than that of AgSD/PVA-AS. Accordingly, the cell cytotoxicity of the AgSD/PVA-WS hydrogels was higher than that of AgSD/PVA-AS. Our study results reveal that e-beam irradiation of PVA solution with dispersed AgSD is a simple and efficient way to prepare AgSD/PVA hydrogels, which might be an ideal antibacterial wound dressing.

Introduction

Burn wounds often suffer bacterial infection caused by gram-positive bacteria like Staphylococcus aureus (S. aureus) or gram-negative bacteria like Escherichia coli (E. coli). Bacterial infection often destroys the skin's protective barrier, thereby rendering the host susceptible to these bacteria delaying or even preventing the skin wound healing. Therefore, to stimulate wound healing and prevent infection, conditions must be established in which microorganisms cannot grow.1, 2, 3 Topical antimicrobial agents are necessary as the avascular necrotic tissues in wounds are rich in exudations and proteins.⁴ The silver sulfadiazine (AgSD), complex is considered as an ideal antibacterial agent for its broad spectrum and 2-fold action on bacterial and fungal cell growth.2, 5 Sulfadiazine can stimulate wound healing and prevent the DNA synthesis by interrupting the production of folate. Whereas silver (Ag) inhibits the bacterial activities by reacting with both the DNA and sulfhydryl groups of bacterial enzymes.4, 5, 6 Existing commercial AgSD products are usually available as a 1% w/w cream.⁷ However, burst release of AgSD into exposed wound areas increases the dosage and frequency of application (about 3 times a day) and lead to inflammation. With long-term use, the excessive application of AgSD cream also results in cytotoxicity toward keratinocytes and fibroblasts.8, 9, 10, 11 Hydrogels containing a high percentage of water can provide an ideal moist environment for tissue regeneration while preventing wound contraction and mitigating the adverse effects of AgSD cream.¹²

Hydrogel wound dressing should (1) protect the wound from secondary damage, (2) have good flexibility, (3) create and maintain a moist environment, (4) absorb wound fluids and exudations, and (5) be biodegradable.13, 14 A variety of methods can be used to fabricate hydrogels including chemical cross-linking, freeze-thawing, and thermal annealing, ultraviolet (UV) radiation and irradiation via gamma or electron beam (e-beam).15, 16, 17, 18 However, chemical cross-linking agents, such as glutaraldehyde and formaldehyde, are potentially hazardous. Freeze-thawing can improve mechanical strength but may reduce its transparency and rate of water absorption. Although not yet fully understood, thermal annealing and UV radiation energy may destroy the native structure and degrade the proteins of polymers.17, 19, 20 E-beam cross-linking is an efficient and biocompatible method for fabricating ideal wound dressing. Polyvinyl alcohol (PVA) is a semi-crystalline polymer produced by the hydrolysis of polyvinyl acetate. In the past few decades, PVA has attracted attention for its high hydrophilicity, good chemical stability, easy processability, and biocompatibility. It has numerous applications, such as tissue engineering scaffolds, wound dressings, controlled release drug delivery systems, and pharmaceutical applications.21, 22, 23, 24

In this study, we fabricated a series of AgSD/PVA hydrogels by e-beam irradiation. We then employed Fourier-transform infrared spectroscopy (FTIR), solid state nuclear magnetic resonance spectroscopy (NMR), and X-ray diffractometer (XRD) to evaluate the chemical structure and crystallinity of AgSD. Finally, we investigated the antibacterial properties, cytotoxicity, and mechanical properties of AgSD/PVA-WS and AgSD/PVA-ammonia solution (AS) with different AgSD contents (0%, 0.25%, 0.5%, 0.75%, 1%, w/w).