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.

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.

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.

Cryostructuring of Polymeric Systems: 62 Preparation and Characterization of Alginate/Chondroitin Sulfate Cryostructurates Loaded with Antimicrobial Substances.

Targeted drug release is a significant research focus in the development of drug delivery systems and involves a biocompatible polymeric carrier and certain medicines. Cryostructuring is a suitable approach for the preparation of efficient macroporous carriers for such drug delivery systems. In the current study, the cryogenically structured carriers based on alginate/chondroitin sulfate mixtures were prepared and their physicochemical properties and their ability to absorb/release the bactericides were evaluated. The swelling parameters of the polysaccharide matrix, the amount of the tightly bound water in the polymer and the sulfur content were measured. In addition, FTIR and UV spectroscopy, optical and scanning microscopy, as well as a standard disk diffusion method for determining antibacterial activity were used. It was shown that alginate/chondroitin sulfate concentration and their ratios were significant factors influencing the swelling properties and the porosity of the resultant cryostructurates. It was demonstrated that the presence of chondroitin sulfate in the composition of a polymeric matrix slowed down the release of the aminoglycoside antibiotic gentamicin. In the case of the NH2-free bactericide, dioxidine, the release was almost independent of the presence of chondroitin sulfate. This trend was also registered for the antibacterial activity tests against the Escherichia coli bacteria, when examining the drug-loaded biopolymeric carriers.

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.

Influence of succinylation of a wide-pore albumin cryogels on their properties, structure, biodegradability, and release dynamics of dioxidine loaded in such spongy carriers.

The goal of this study was to reveal how the chemical modification, succinylation in this case, of the wide-pore serum-albumin-based cryogels affects on their osmotic characteristics (swelling extent), biodegradability and ability to be loaded with the bactericide substance - dioxidine, as well as on its release. The cryogels were prepared via the cryogenic processing (freezing - frozen storage - thawing) of aqueous solutions containing bovine serum albumin (50 g/L), denaturant (urea or guanidine hydrochloride, 1.0 mol/L) and reductant (cysteine, 0.01 mol/L). Freezing/frozen storage temperatures were either -15, or -20, or -25 °C. After defrosting, spongy cryogels were obtained that possessed the system of interconnected gross pores, whose shape and dimensions were dependent on the freezing temperature and on the type of denaturant introduced in the feed solution. Subsequent succinylation of the resultant cryogels caused the growth of the swelling degree of the pore walls of these spongy materials, resulted in strengthening of their resistance against of trypsinolysis and gave rise to an increase in their loading capacity with respect to dioxidine. With that, the microbiological tests showed a higher bactericidal activity of the dioxidine-loaded sponges based on the succinylated albumin cryogels as compared to that of the drug-carriers based on the non-modified protein sponges.

Chiral Plasmonic Biosensors.

Biosensing requires fast, selective, and highly sensitive real-time detection of biomolecules using efficient simple-to-use techniques. Due to a unique capability to focus light at nanoscale, plasmonic nanostructures provide an excellent platform for label-free detection of molecular adsorption by sensing tiny changes in the local refractive index or by enhancing the light-induced processes in adjacent biomolecules. This review discusses the opportunities provided by surface plasmon resonance in probing the chirality of biomolecules as well as their conformations and orientations. Various types of chiral plasmonic nanostructures and the most recent developments in the field of chiral plasmonics related to biosensing are considered.