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.

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.

Three types of copper derivatives formed by CuCl2·2H2O interaction with (Z)-3-aryl-2-(methylthio)-5-(pyridine-2-ylmethylene)-3,5-dihydro-4H-imidazol-4-ones.

The reactions of (Z)-3-aryl-2-(methylthio)-5-(pyridine-2-ylmethylene)-3,5-dihydro-4H-imidazol-4-ones (3) with CuCl2·2H2O in the presence of a reducing solvent (alcohol or dimethylformamide (DMF)) produce three types of Cu-containing compounds: two Cu complexes with a composition of CuII(3)Cl2 (4) and CuI(3)Cl (5) as well as a salt (3 + H)+CuICl2- (6) in a 4 : 5 : 6 ratio depending on the substituent at the N(3) nitrogen atom of the ligand moiety. In non-reducing solvents (dimethyl sulfoxide (DMSO) and CHCl3/acetone), only complexes 4 were formed, All three Cu derivatives (4, 5, and 6) were characterized by single-crystal X-ray diffraction, UV/vis spectroscopy, and electrochemistry data. Convenient electrochemical and UV-vis spectral criteria were recorded, which made it possible to distinguish between the different Cu-containing compounds. Based on the electron spectroscopy and electron paramagnetic resonance (EPR) data, a possible scheme for the formation of compounds 4-6 was proposed, including the initial coordination of copper(ii) chloride with an organic ligand, the subsequent reduction of the resulting complex 4 by DMF with the formation of salt 6, and the further transition of salt 6 into the complex 5.

Femtosecond spectroscopy and TD-DFT calculations of CuCl4(2-) excited states.

Photoinduced processes of tetrahexylammonium tetrachlorocuprate [(C6H13)4N]2Cu(II)Cl4 in chloro-organic solvents were investigated by steady state photolysis and femtosecond transient absorption spectroscopy. The quantum yield of photoreduction of CuCl4(2-) was estimated to be about 1%; the process resulted in the formation of the copper(i) chlorocomplex Cu(I)Cl3(2-) and a chlorine atom. Femtosecond laser photolysis with a 422 nm, 40 fs pulse revealed a three-exponential decay of the LMCT excited state of [(C6H13)4N]2CuCl4. A global fitting SVD analysis of the femtosecond transient spectra suggested three relaxation times, ∼400 fs, ∼1.4 ps and ∼5.8 ps. Oscillations in transient absorption kinetic traces were documented for CuCl4(2-) solutions in 2-chlorobutane. The oscillation Fourier transform analysis of the oscillations and linear predictive singular value decomposition revealed peaks at 283 cm(-1) (damping time ∼600 fs) and 181 cm(-1) (damping time ∼400 fs). These peaks can be tentatively attributed to νs(Cu-Cl) symmetric stretching frequency A1 and T2 reflecting excited state vibrational coherence. Quantum chemical calculations suggest a possible scheme for relaxation pathways in CuCl4(2-). The observed transient excited state absorption bands agree semiquantitatively with the calculated transition bands of CuCl4(2-).