Green Synthesis of Metal and Metal Oxide Nanoparticles: A Review of the Principles and Biomedical Applications.

In recent years, interest in nanotechnology has increased exponentially due to enhanced progress and technological innovation. In tissue engineering, the development of metallic nanoparticles has been amplified, especially due to their antibacterial properties. Another important characteristic of metal NPs is that they enable high control over the features of the developed scaffolds (optimizing their mechanical strength and offering the controlled release of bioactive agents). Currently, the main concern related to the method of synthesis of metal oxide NPs is the environmental impact. The physical and chemical synthesis uses toxic agents that could generate hazards or exert carcinogenicity/environmental toxicity. Therefore, a greener, cleaner, and more reliable approach is needed. Green synthetic has come as a solution to counter the aforementioned limitations. Nowadays, green synthesis is preferred because it leads to the prevention/minimization of waste, the reduction of derivatives/pollution, and the use of non-toxic (safer) solvents. This method not only uses biomass sources as reducing agents for metal salts. The biomolecules also cover the synthesized NPs or act as in situ capping and reducing agents. Further, their involvement in the formation process reduces toxicity, prevents nanoparticle agglomeration, and improves the antimicrobial activity of the nanomaterial, leading to a possible synergistic effect. This study aims to provide a comprehensive review of the green synthesis of metal and metal oxide nanoparticles, from the synthesis routes, selected solvents, and parameters to their latest application in the biomedical field.

Synergic Effect of Honey with Other Natural Agents in Developing Efficient Wound Dressings.

Honey has been used for therapeutic and nutritional purposes since ancient times. It was considered one of the essential medical assets in wound healing. According to research, honeybees have significant antibacterial, antioxidant, anti-inflammatory, antitumor, and wound-healing properties. Lately, scientific researchers have focused on apitherapy, using bee products to protect and strengthen the immune system. Since honey is the most important natural product rich in minerals, proteins, and vitamins, it has been intensively used in such therapies. Honey has gained significant consideration because of the beneficial role of its antioxidant compounds, such as enzymes, proteins, amino and organic acids, polyphenols, and carotenoids, but mainly due to flavonoids and phenolic acids. It has been proven that phenolic compounds are responsible for honey's biological activity and that its physicochemical properties, antioxidants, and antimicrobial potential are significant for human health. The review also presents some mechanisms of action and the medical applications of honey, such as wound healing dressings, skin grafts, honey-based nanofibers, and cochlear implants, as the most promising wound healing tools. This extensive review has been written to highlight honey's applications in medicine; its composition with the most important bioactive compounds also illustrates its synergistic effect with other natural products having remarkable therapeutic properties in wound healing.

Iron Oxide-Silica Core-Shell Nanoparticles Functionalized with Essential Oils for Antimicrobial Therapies.

Recent years have witnessed a tremendous interest in the use of essential oils in biomedical applications due to their intrinsic antimicrobial, antioxidant, and anticancer properties. However, their low aqueous solubility and high volatility compromise their maximum potential, thus requiring the development of efficient supports for their delivery. Hence, this manuscript focuses on developing nanostructured systems based on Fe3O4@SiO2 core-shell nanoparticles and three different types of essential oils, i.e., thyme, rosemary, and basil, to overcome these limitations. Specifically, this work represents a comparative study between co-precipitation and microwave-assisted hydrothermal methods for the synthesis of Fe3O4@SiO2 core-shell nanoparticles. All magnetic samples were characterized by X-ray diffraction (XRD), gas chromatography-mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetry and differential scanning calorimetry (TG-DSC), and vibrating sample magnetometry (VSM) to study the impact of the synthesis method on the nanoparticle formation and properties, in terms of crystallinity, purity, size, morphology, stability, and magnetization. Moreover, the antimicrobial properties of the synthesized nanocomposites were assessed through in vitro tests on Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. In this manner, this study demonstrated the efficiency of the core-shell nanostructured systems as potential applications in antimicrobial therapies.

MAPLE Coatings Embedded with Essential Oil-Conjugated Magnetite for Anti-Biofilm Applications.

The present study reports on the development and evaluation of nanostructured composite coatings of polylactic acid (PLA) embedded with iron oxide nanoparticles (Fe3O4) modified with Eucalyptus (Eucalyptus globulus) essential oil. The co-precipitation method was employed to synthesize the magnetite particles conjugated with Eucalyptus natural antibiotic (Fe3O4@EG), while their composition and microstructure were investigated using grazing incidence X-ray diffraction (GIXRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The matrix-assisted pulsed laser evaporation (MAPLE) technique was further employed to obtain PLA/Fe3O4@EG thin films. Optimal experimental conditions for laser processing were established by complementary infrared microscopy (IRM) and scanning electron microscopy (SEM) investigations. The in vitro biocompatibility with eukaryote cells was proven using mesenchymal stem cells, while the anti-biofilm efficiency of composite PLA/Fe3O4@EG coatings was assessed against Gram-negative and Gram-positive pathogens.

Biodistribution of essential oil-conjugated silver nanoparticles.

The beneficial synergy between antimicrobial silver nanoparticles (AgNPs) and essential oils (EOs), with therapeutic effects that have been acknowledged and explored for a long time, opens the way towards developing new and promising alternatives for anti-infective therapies. With the aim to improve the cytocompatibility and stability of AgNPs and to overcome the volatilization of EOs, AgNPs conjugated with sage (Salvia officinalis) and cinnamon (Cinnamomum aromaticum) EOs were obtained in our study. The synthesis process was realized either by classical or ultrasound-assisted chemical reduction. Compositional and microstructural characterization of the as-obtained Ag@EO NPs was performed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The biodistribution of Ag@EO NPs was evaluated on a mouse animal model.

Multifunctional Platforms Based on Graphene Oxide and Natural Products.

Background and objectives: In the last few years, graphene oxide has attracted much attention in biomedical applications due to its unique physico-chemical properties and can be used as a carrier for both hydrophilic and/or hydrophobic biomolecules. The purpose of this paper was to synthesize graphene oxide and to obtain multifunctional platforms based on graphene oxide as a nanocarrier loaded with few biologically active substances with anticancer, antimicrobial or anti-inflammatory properties such as gallic acid, caffeic acid, limonene and nutmeg and cembra pine essential oils. Materials and Methods: Graphene oxide was obtained according to the method developed by Hummers and further loaded with biologically active agents. The obtained platforms were characterized using FTIR, HPLC, TGA, SEM, TEM and Raman spectroscopy. Results: Gallic acid released 80% within 10 days but all the other biologically active agents did not release because their affinity for the graphene oxide support was higher than that of the phosphate buffer solution. SEM characterization showed the formation of nanosheets and a slight increase in the degree of agglomeration of the particles. The ratio I2D/IG for all samples was between 0.18 for GO-cembra pine and 0.27 for GO-limonene, indicating that the GO materials were in the form of multilayers. The individual GO sheets were found to have less than 20 µm, the thickness of GO was estimated to be ~4 nm and an interlayer spacing of about 2.12 Å. Raman spectroscopy indicated that the bioactive substances were adsorbed on the surface and no degradation occurred during loading. Conclusions: These findings encourage this research to further explore, both in vitro and in vivo, the biological activities of bioactive agents for their use in medicine.

Evaluation and Exploitation of Bioactive Compounds of Walnut, Juglans regia.

In the last few years, great importance has been given to natural materials (such as walnuts, peanuts, chestnuts) due to their medicinal and pharmaceutical uses induced by the presence of natural agents, including polyphenols. Juglans regia is a traditional plant that has been used since ancient times in traditional medicine for the treatment of various diseases like microbial infections, stomach ache, thyroid dysfunctions, cancer, heart diseases and sinusitis. Recently, scientific attention for the phytochemical profile of walnut by-products is increasing due to their valuable active constituents. Natural polyphenols are important compounds present in walnut with valuable properties that have been studied for the treatment of inflammation, cancer or anti-ageing effect. The use of nanocarriers as a drug delivery system is now a promising strategy to get more stable products and is easier to apply in a medical, therapeutic and pharmaceutical environment. The aim of this work was to review the latest information provided by scientific investigators regarding the nutritional value, bioactive compounds, antioxidant and antitumor activity of walnut by-product extracts. Moreover, this review provides comprehensive information on the nanoencapsulation of bioactive constituents for application in clinical medicine, particularly in cancer research.

Manufacturing nanostructured chitosan-based 2D sheets with prolonged antimicrobial activity.

The purpose of this study was to synthesize, characterize and test the antimicrobial and antifungal activity of chitosan-based hydrogels containing metal (silver - Ag) and oxide (zinc oxide - ZnO) nanoparticles (NPs) but also natural compounds such as usnic acid (UA). The two-dimensional (2D) sheets were obtained by electrospinning technique, with the aim to produce multifunctional wound dressing with regenerative and even anti-infective roles. The most important advantages of the electrospinning technique are related to the possibility of obtaining fibers with controlled morphology, usually having high specific surface and water and air penetration and the possibility of functionalizing these fibers and nets depending on the desired application. These advantages make it possible to use electrospinning for a wide range of biomedical applications, such as tissue engineering, controlled release, implantology, wound healing, and more. The obtained composite materials were characterized by infrared (IR) spectroscopy and scanning electron microscopy (SEM) and tested against common pathogens: Pseudomonas aeruginosa (Gram-negative staining), Staphylococcus aureus (Gram-positive staining) and Candida albicans (fungus).

Antimicrobial coatings based on zinc oxide and orange oil for improved bioactive wound dressings and other applications.

This work presents a novel nano-modified coating for wound dressings and other medical devices with anti-infective properties, based on functionalized zinc oxide nanostructures and orange oil (ZnO@OO). The obtained nanosurfaces were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), selected area electron diffraction (SAED), differential thermal analysis-thermogravimetry (DTA-TG), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) spectroscopy. The obtained nanocomposite coatings exhibited an antimicrobial activity superior to bare ZnO nanoparticles (NPs) and to the control antibiotic against Staphylococcus aureus and Escherichia coli, as revealed by the lower minimal inhibitory concentration values. For the quantitative measurement of biofilm-embedded microbial cells, a culture-based, viable cell count method was used. The coated wound dressings proved to be more resistant to S. aureus microbial colonization and biofilm formation compared to the uncoated controls. These results, correlated with the good in vivo biodistribution open new directions for the design of nanostructured bioactive coating and surfaces, which can find applications in the medical field, for obtaining improved bioactive wound dressings and prosthetic devices, but also in food packaging and cosmetic industry.

Magnetite nanostructures functionalized with cytostatic drugs exhibit great anti-tumoral properties without application of high amplitude alternating magnetic fields.

Here, we report the synthesis, characterization and the impact of magnetite nanoparticles functionalized with cytostatic drugs, epirubicin (Epi) and fludarabine (Flu) (Fe3O4@Epi, Fe3O4@Flu) prepared by chemical co-precipitation method on tumoral cells in vitro. The average diameter of the resulted particles was about 4 nm for both Fe3O4@Epi and for Fe3O4@Flu. These bioactive nanostructured materials proved to significantly enhance the antitumor effect of tested cytostatic drugs in vitro. The most significant result was obtained in the case of Epi, where the tested magnetite nanostructured material enhanced the cytotoxic effect of this drug with more than 50%.

In vivo evaluation of Fe3O4 nanoparticles.

Our review summarizes the latest approaches regarding in vivo biocompatibility evaluation of magnetite nanoparticle-based systems. The paper follows the applications of Fe3O4 nanoparticles in cancer diagnosis and treatment, by means of nanoparticle-mediated magnetic hyperthermia, respectively by targeted delivery of chemotherapeutics. The long-term biodistribution in relevant organisms is also discussed, due to the need of knowing the exact course of magnetite nanoparticles after the fulfillment of their function. Several commercial Fe3O4 systems used as contrast agents for medical imaging and cancer treatment by hyperthermia are briefly presented in the last section.