Antibiotics, Vol. 12, Pages 59: Magnetite-Based Nanostructured Coatings Functionalized with Nigella sativa and Dicloxacillin for Improved Wound Dressings

Wound management is an important clinical issue worldwide [1,2,3,4,5]. According to the report published by Fortune Business Insights Pvt. Ltd., the global wound care market is projected to grow from 18.51 billion USD in 2022 to 28.23 billion by 2029 [6]. In the whole wound healing process, wound dressings have a crucial role. The main characteristics of an efficient dressing are to reduce the risk of infection, minimize the pain, apply compression, protect the wound from secondary injury, facilitate the removal of excess exudate, and promote better and rapid healing [7,8].The wound site is a suitable environment for the colonization and proliferation of viruses, bacteria, or fungi. Normally, these pathogens are overtaken and eliminated by white blood cells and other components of the immune system, but there are many cases when the body’s defence mechanism is overcome and chronic infections associated with the formation of (mono-or polymicrobial) biofilms appear [9]. By focusing on microbial cell walls or membranes, cellular respiration processes, or quorum sensing systems, natural substances have demonstrated their effectiveness in relation to the present antibiotic resistance issue [10]. The enhanced hydrophobicity, volatility, lipophilicity, oxidation sensitivity, and lower solubility and stability of natural substances, however, pose a number of challenges despite their enormous promise [11]. Therefore, their cooperation with nanotechnology-based strategies is required to prevent the advancement of microbial diseases.

Recent developments in the wound care management domain are focused on dressings containing drugs, including antibiotics/antimicrobials, as an excellent solution in speeding up wound healing, protecting against infections, and in tissue regeneration. Progress has been made in obtaining wound dressings with demonstrated antimicrobial efficiency with the help of nanotechnological tools—nanoparticles (NPs) possessing antimicrobial properties and being used as drug carriers.

The use of metal and metal oxide NPs (including magnetite—Fe3O4) in combination with antibiotics and/or natural active substances as antimicrobial agents has specifically concentrated on the wound management area [12]. Fe3O4 NPs were previously functionalised with different antibiotics such as cefepim, streptomycin, and neomycin [13], which have been applied and tested on different infection microorganisms. In the case of natural substances, there are several works regarding Fe3O4 NPs functionalised with natural substances for the use in wound dressing applications. For example, Anghel et al. investigated the efficiency of a novel wound dressing coating containing Fe3O4 and Satureja hortensis essential oil. The wound dressings exhibited improved antimicrobial properties, preventing Candida albicans colonization and biofilm development [14]. The aim of a study by Radulescu et al. was to develop a biocompatible and antiinfection coating for wound dressings, containing Fe3O4 NPs functionalized with patchouli essential oil in order to impart antimicrobial properties to the dressings [15]. In another study by Chircov et al., the research group developed nanostructured systems based on Fe3O4@SiO2 core–shell NPs and three different types of essential oils, i.e., thyme, rosemary, and basil, to be potentially used in wound antimicrobial therapies. The antimicrobial properties of the synthesized nanocomposites were assessed by in vitro tests on Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans [16].These NPs have significant potential for the administration of pharmacological substances, as they can enhance biocompatibility, ensure targeted, controlled, and prolonged release of therapeutic compounds, and reduce the amount of bioactive compounds needed for the therapeutic effect desired in many biomedical applications [17,18,19,20,21]. Fe3O4 NPs properties (such as high surface area, size and size distribution) are closely related to the synthesis method applied to produce them (ex: co-precipitation [22,23,24], sol-gel [25,26], microemulsion [27,28], sonochemical [29], hydrothermal [30,31], electrochemical [32], thermal decomposition [33], polyol [34,35], and biological synthesis [36,37], etc.). The antimicrobial nature of the Fe3O4 NPs can be obtained by anchoring the therapeutic agent of interest [38,39]. In wound care management, Fe3O4 NPs, which act as vectors for the active substances, must ensure a slow, continuous drug delivery and release and avoid the evaporation and absorbance of active components in the dressings’ texture [40].Dicloxacillin sodium monohydrate (DCX), a semisynthetic isoxazolyl penicillin, exhibits antimicrobial activity against a wide variety of Gram-positive bacteria, as well as stability against penicillinases and a low level of toxicity [41]. DCX has shown activity against Stafiloccocus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitides [42,43,44]. It is currently applied with success in the treatment of bacterial infections such as bone, ear, skin, urinary tract infections, and pneumonia [45,46]. Nigella sativa seeds have been used in many ancient cultures due to their high content of biologically active essential oils to treat skin diseases, gastric and heart conditions, pulmonary illnesses, various infections, diabetic wounds, etc. [47,48,49,50,51]. Nevertheless, seeds/powder (PNS) and oils (NS) of N. sativa are well known for their anticancer [52,53], antimicrobial [54,55], anti-inflammatory [56], antioxidant [57], glucose lowering [58,59], antihistaminic [60], immune booster [61,62], antiparasitic [63], and hepatoprotective properties [64,65,66]. The biofilm inhibition effectiveness of NS compounds was proved against various human pathogenic microorganisms. It has been revealed that NS active substances displayed a considerable bactericidal activity against S. aureus [51,67,68], S. epidermidis, and Enterococcus faecalis biofilm growth and development [69]. N. sativa essential oil and its active compounds, thymoquinone and carvacrol, modulate antibiotic resistance in Listeria monocytogenes against various antimicrobials [70]. Furthermore, we noted the isolation of multi-drug resistant S. aureus from diabetic wounds and that more than half of isolates were susceptible to different concentrations of N. sativa oil [51].

Ultimately, by merging the above-mentioned ideas, we report on the deposition of nanostructured coatings from Fe3O4 functionalized with dicloxacillin (DCX) antibiotic and Nigella Sativa essential oil (NS) or powder (PNS) by matrix assisted pulsed laser evaporation (MAPLE). The novelty of our work consists in obtaining wound dressing coatings which benefit from the combined effects of both natural substances and antibiotics which are delivered by nanostructured vectors. The scope of our work is to obtain improved wound dressings and to have a double outcome: (i) a reduction in microbial contamination and (ii) the promotion of wound healing.

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