Protein-reduced gold nanoparticles mixed with gentamicin sulfate and loaded into konjac/gelatin sponge heal wounds and kill drug-resistant bacteria
Introduction
Skin trauma is one of the most common injuries in real life that occurs mostly due to accidents [1]. Injured skin can be easily infected by various pathogens, which can cause inflammation and infection, and retard wound healing [2]. Wound dressings can relieve the symptoms of wound infection. A good wound dressing should be non-toxic, non-allergenic, and biocompatible [3]. In addition, a certain extent of moisture is conducive for wound healing; hence, a wound dressing should be capable of maintaining a moist environment in the vicinity of the wound [4,5]. Furthermore, wound dressings should also possess excellent antibacterial properties to prevent bacterial invasion [6,7].
The overuse of antibiotics has led to the emergence of superbugs and antibiotic resistance, thereby weakening the bactericidal effects of antibiotics at concentrations at which they were previously effective [8]. Multidrug-resistant pathogens can lead to the re-emergence of many lethal but incurable diseases, and also pose a threat to human life and health [9]. To circumvent this problem, certain inorganic nanoparticles (NPs), such as Ag NPs, Cu NPs, and ZnO NPs have been used for developing antibacterials. Studies have shown that these NPs not only possess excellent antibacterial ability, but are also refractory to the development of antibiotic resistance [[10], [11], [12]]. However, several reports have demonstrated the cytotoxicity of Ag NPs, Cu NPs, and ZnO NPs toward different mammalian cells [[13], [14], [15], [16]]. Another alternative involves elimination of superbugs by amplifying the antibacterial effect of antibiotics. Studies have shown that Au NPs can enhance the bactericidal ability of antibiotics, such as carbapenems [17], levofloxacin [18], and streptomycin [19]. NPs are used as drug carriers that improve dissolution and enhance absorption of drugs, increase drug targeted performance, control drug release, and reduce side effects [[20], [21], [22]]. In addition, studies have also shown that the higher the surface-area-to-volume ratio of Au NPs, the stronger the amplification effect on antibiotics [23]. Furthermore, Au NPs themselves are non-cytotoxic and antibacterial in nature [24,25]. Au NPs can also be efficiently produced by the reduction of auric chloride acid (HAuCl4) by various chemical reagents, such as sodium citrate, sodium borohydride, and ascorbic acid [[26], [27], [28]]. However, these reductants have some disadvantages of polluting the environment, harming the human body, and being expensive [29]. Therefore, it is of great significance to find a simple, inexpensive, and green Au NP synthesis method. Proteins can act as reductants and stabilizers for high-fluorescence Au NPs. [30]. Egg white, which is a rich source of proteins, is biocompatible and possesses foaming, emulsifying, and adhesive abilities, enabling it to improve water retention of dressings and maintain moisture content in wounds [31,32]. Furthermore, it is inexpensive and abundant. Therefore, use of egg white as a green reduction system for preparing small-size Au NPs that can amplify the antibacterial effect of antibiotics is an effective method for eliminating superbugs. Gentamycin sulfate (GS), an aminoglycoside antibiotic, possesses many advantages such as good water solubility and wide antimicrobial spectrum, can be used to treat gram-negative as well as gram-positive bacterial infections, is less costly, and elicits low side effects [33,34]. The amine groups (NH2) in GS and Au NPs are connected by hydrogen bonds, and their combination improves the antibacterial efficiency of GS. Therefore, Au NPs amplify the antibacterial activity of GS and may effectively kill superbugs [35].
In the wound dressing area, in addition to good antibacterial properties, dressings provide a moist environment for the wound. Gelatin is a natural polymer, which has been widely used in the pharmaceutical industry [36] and has good biocompatibility. However, the mechanical properties of gelatin deteriorate after freeze-drying, and its water absorption capacity is weak. KGM is a natural polysaccharide of high molecular weight, which has good biodegradability and biocompatibility [37]. KGM is rich in hydroxyl and carbonyl groups; hence, it can utilize hydrogen bonds and van der Waals forces to attract water molecules and maintain moisture content [38,39]. The addition of KGM to gelatin can increase the mechanical and water retention properties of materials [40]. Furthermore, KGM/gelatin does not cause secondary damage to the wound, and effectively improves the material's water absorption, water retention, and mechanical properties.
In this study, we used two steps to prepare KGM/Gelatin@Au NPs/GS for treating skin trauma. The egg white reducer was used to prepare Au NP solution, followed by dissolution of KGM and gelatin, and finally freeze-drying. Fig. 1 clearly shows the KGM/gelatin @ preparation process of the Au NPs/GS and the sterilization principle. KGM/gelatin@Au NPs/GS was studied using X-ray diffraction spectrometry (XRD) and scanning electron microscopy (SEM), and its mechanical properties were assessed. We used Escherichia coli and Staphylococcus aureus to determine the antibacterial activity of KGM/Gelatin@Au NPs/GS. Further, we used animal wound healing experiments and histopathological examination to evaluate the healing of wounds treated with KGM/Gelatin@Au NPs/GS.
Section snippets
Materials
KGM was purchased from Chongqing West konjac Technical Developing Company (Chongqing, China). Gelatin was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China). Auric chloride acid (HAuCl4) was purchased from Sinopharm Limited by Share Ltd. (Beijing, China). Eggs were purchased from Chongqing Zhengda agricultural food limited company (Chongqing China). GS was procured from Chongqing DUCAM Yangtze River Pharmaceutical Co. Ltd. (Chongqing, China). S. aureus
FTIR analysis
Fig. 2A shows the IR spectra for films of KGM-mixed gelatin sponge with different substances in the wavelength range of 4000–400 cm−1. The characteristic absorption bands of mannose in KGM appeared at 810 and 877 cm−1, corresponding to β-1,4-linked glycosidic bond and pyranoid group, respectively. The characteristic absorption band of the C6-OH group in KGM appeared at 1133 cm−1. The peaks at 3419 and 2912 cm−1 were caused by vibrations of hydroxyl (OH) and methyl groups (CH3) in KGM,
Conclusion
In this study, to prepare a wound dressing with high antibacterial properties, KGM and gelatin were mixed and loaded with Au NPs and GS to prepare the sponge KGM/Gelatin@Au NPs/GS, which enhanced the water retention capacity of pure KGM/Gelatin and still exhibited good water absorption properties. This sponge also possessed better mechanical properties and antibacterial properties. Good water absorption and retention performance ensured that the wound was clean, and created and maintained a
Acknowledgements
This work was supported by the National Science Foundation of China (NO. 51803171), the Key Research and Natural Development Program (Social Development) of Zhenjiang City (NO. SH2018001) and the Fundamental Research Funds for the Central Universities (No. XDJK2020B017).
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