Hybrid Nanosystems of Antibiotics with Metal Nanoparticles—Novel Antibacterial Agents

The appearance and increasing number of microorganisms resistant to the action of antibiotics is one of the global problems of the 21st century. Already, the duration of therapeutic treatment and mortality from infectious diseases caused by pathogenic microorganisms have increased significantly over the last few decades. Nanoscale inorganic materials (metals and metal oxides) with antimicrobial potential are a promising solution to this problem. Here we discuss possible mechanisms of pathogenic microorganisms’ resistance to antibiotics, proposed mechanisms of action of inorganic nanoparticles on bacterial cells, and the possibilities and benefits of their combined use with antibacterial drugs. The prospects of using metal and metal oxide nanoparticles as carriers in targeted delivery systems for antibacterial compositions are also discussed

Nanoparticles of Bioactive Metals/Metal Oxides and Their Nanocomposites with Antibacterial Drugs for Biomedical Applications

The increasing appearance of new strains of microorganisms resistant to the action of existing antibiotics is a modern problem that requires urgent decision. A promising potential solution is the use of nanoparticles of bioactive metals and their oxides as new antibacterial agents, since they are capable of affecting pathogenic microorganisms by mechanisms different from the mechanisms of action of antibiotics. Inorganic nanoparticles possess a wide spectrum of antibacterial activity. These particles can be easily conjugated with drug molecules and become carriers in targeted drug-delivery systems. This paper discusses the benefits and prospects of the application of nanoparticles from metals and metal oxides and their nanocomposites with antibacterial drugs

Metal and Metal Oxides Nanoparticles and Nanosystems in Anticancer and Antiviral Theragnostic Agents

The development of antiviral treatment and anticancer theragnostic agents in recent decades has been associated with nanotechnologies, and primarily with inorganic nanoparticles (INPs) of metal and metal oxides. The large specific surface area and its high activity make it easy to functionalize INPs with various coatings (to increase their stability and reduce toxicity), specific agents (allowing retention of INPs in the affected organ or tissue), and drug molecules (for antitumor and antiviral therapy). The ability of magnetic nanoparticles (MNPs) of iron oxides and ferrites to enhance proton relaxation in specific tissues and serve as magnetic resonance imaging contrast agents is one of the most promising applications of nanomedicine. Activation of MNPs during hyperthermia by an external alternating magnetic field is a promising method for targeted cancer therapy. As therapeutic tools, INPs are promising carriers for targeted delivery of pharmaceuticals (either anticancer or antiviral) via magnetic drug targeting (in case of MNPs), passive or active (by attaching high affinity ligands) targeting. The plasmonic properties of Au nanoparticles (NPs) and their application for plasmonic photothermal and photodynamic therapies have been extensively explored recently in tumor treatment. The Ag NPs alone and in combination with antiviral medicines reveal new possibilities in antiviral therapy. The prospects and possibilities of INPs in relation to magnetic hyperthermia, plasmonic photothermal and photodynamic therapies, magnetic resonance imaging, targeted delivery in the framework of antitumor theragnostic and antiviral therapy are presented in this review

Metal Nanoparticle Containing Nanocomposites of Drug Substances and Their Potential Biomedical Applications

New hybrid nanosystems containing the antibacterial substances dioxidine or gentamicin sulfate with bioactive metal (Ag, Cu) nanoparticles have been obtained by a cryogenic freeze-drying method and incorporate further the nanocomposites thus obtained into the cryogenically structured biopolymeric matrices based on gelatin, calcium alginate, and chitosan. FTIR, UV-visible, and NMR spectroscopy, TEM and SEM microscopy data show that the resulting systems consist of wide-porous polymer sponges (pore diameters, 10–200 μm) that contain antibacterial drugs and silver (2–30 nm) or copper (1–5 nm) nanoparticles. The investigation showed that these systems ensure a gradual release of dioxidine (from 40 min up to 3 days), depending on the nature of the matrix and its microstructure. The higher activity of hybrid composites based on nanometals and dioxidine or incorporated into cryostructured biopolymer matrices against the bacterial strains of Escherichia coli 52, Staphylococcus aureus 144 is demonstrated as compared to the individual components in the same matrices

Cryochemical Production of Drug Nanoforms: Particle Size and Crystal Phase Control of the Antibacterial Medication 2,3-Quinoxalinedimethanol-1,4-dioxide (Dioxidine)

Increasing the effectiveness of known, well-tested drugs is a promising low-cost alternative to the search for new drug molecular forms. Powerful approaches to solve this problem are (a) an active drug particle size reduction down to the nanoscale and (b) thermodynamically metastable but kinetically stable crystal modifications of drug acquisition. The combined cryochemical method has been used for size and structural modifications of the antibacterial drug 2,3-quinoxalinedimethanol-1,4-dioxide (dioxidine). The main stage of the proposed technique includes the formation of a molecular vapor of the drug substance, combined with a carrier gas (CO2) flow, followed by a fast condensation of the drug substance and CO2 molecules on a cooled-by-liquid nitrogen surface of preparative cryostate. It was established that the molecular chemical structure of the drug substance remained unchanged during cryochemical modification; however, it led to a significant decrease of the drug particles’ size down to nanosizes and changes in the crystal structures of the solid drug nanoforms obtained. Varying carrier gas (CO2) flow led to changes in their solid phase composition. A higher dissolution rate and changes in antibacterial activity were demonstrated for cryomodified dioxidine samples in comparison to the properties of the initial pharmacopeia dioxidine

Cryochemically Obtained Nanoforms of Antimicrobial Drug Substance Dioxidine and Their Physico-chemical and Structural Properties

Nanoforms of the antimicrobial drug substance 2,3-bis-(hydroxymethyl) quinoxaline-N,N′-dioxide with particles sizes between 50 and 300 nm were obtained by cryochemical modification of the initial pharmaceutical substance using a freeze-drying technique and were characterized by different physicochemical methods (FTIR, UV-Vis, 1H-NMR, DSC, TG and X-ray diffraction) and transmission electron microscopy (TEM). The data obtained from FTIR- and UV–Vis-spectroscopy confirmed the unaltered chemical structure of dioxidine molecules due to the cryochemical modification method. At the same time, X-ray diffraction and thermal analysis data show the change of the crystal structure compared to the parameters of the initial pharmaceutical dioxidine substance. A higher dissolution rate was revealed for cryomodified dioxidine nanoforms. The existence of three polymorphic crystal phases was established for cryomodified dioxidine samples possessed by some thermal activation processes: two anhydrous polymorphic phases, triclinic (T) and monoclinic (M), and one hydrated form (H)

Pharmaceutical Nanoparticles Formation and Their Physico-Chemical and Biomedical Properties

The use of medicinal substances in nanosized forms (nanoforms, nanoparticles) allows the therapeutic effectiveness of pharmaceutical preparations to be increased due to several factors: (1) the high specific surface area of nanomaterials, and (2) the high concentration of surface-active centers interacting with biological objects. In the case of drug nanoforms, even low concentrations of a bioactive substance can have a significant therapeutic effect on living organisms. These effects allow pharmacists to use lower doses of active components, consequently lowering the toxic side effects of pharmaceutical nanoform preparations. It is known that many drug substances that are currently in development are poorly soluble in water, so they have insufficient bioavailability. Converting them into nanoforms will increase their rate of dissolution, and the increased saturation solubility of drug nanocrystals also makes a significant contribution to their high therapeutic efficiency. Some physical and chemical methods can contribute to the formation of both pure drug nanoparticles and their ligand or of polymer-covered nanoforms, which are characterized by higher stability. This review describes the most commonly used methods for the preparation of nanoforms (nanoparticles) of different medicinal substances, paying close attention to modern supercritical and cryogenic technologies and the advantages and disadvantages of the described methods and techniques; moreover, the improvements in the physico-chemical and biomedical properties of the obtained medicinal nanoforms are also discussed