Hydroxyapatite-biopolymers-ZnO composite with sustained Ceftriaxone release as a drainage system for treatment of purulent cavities.

Composite based on nano-sized hydroxyapatite (HA), zinc oxide (ZnO), chitosan (CS), alginate (Alg) with the function of sustained Ceftriaxone (CF) release was created as molecular sorption-aspiration drainage system (SADS), designed for the treatment of purulent cavities of various genesis, including peritonitis. ZnO stabilizes the composite structurally, reducing the swelling by 1.5 and porosity by 1.4 times. The absorption of tryptophan (Trp) by SADS for 72 h from aqueous solution is 80%, while from PBS - 50%. The content of ZnO (15,20%) slows the CF release by 1.6 times on the first day of SADS installation and reduces the likelihood of "burst" drug release. CF release exponent of ZnO-containing composites indicates the non-Fickian diffusion kinetics. 20%ZnO-containing composite is closest to zero-order kinetics. The reduction of the concentration of E. coli microbial cells for 43% in the presence of HA-nZnO-Alg/CS -based CADS and positive therapeutic pathomorphosis were observed in vivo.

C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes.

BACKGROUND: C60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C60 fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. The main aim of this study was to investigate the effect of C60 fullerene and its nanocomplexes with anticancer drugs on human phagocyte metabolic profile in vitro. METHODS: Analysis of the metabolic profile of phagocytes exposed to C60 fullerene in vitro revealed augmented phagocytic activity and down-regulated reactive nitrogen species generation in these cells. Additionally, cytofluorimetric analysis showed that C60 fullerene can exert direct cytotoxic effect on normal and transformed phagocytes through the vigorous induction of intracellular reactive oxygen species generation. RESULTS: Cytotoxic action as well as the pro-oxidant effect of C60 fullerene was more pronounced toward malignant phagocytes. At the same time, C60 fullerenes have the ability to down-regulate the pro-oxidant effect of cisplatin on normal cells. These results indicate that C60 fullerenes may influence phagocyte metabolism and have both pro-oxidant and antioxidant properties. CONCLUSIONS: The antineoplastic effect of C60 fullerene has been observed by direct toxic effect on tumor cells, as well as through the modulation of the functions of effector cells of antitumor immunity.

The Complexation of the Anticancer Drug ThioTEPA with Methylated DNA Base Guanine: Combined Ab Initio and QTAIM Investigation.

Non-covalent complexes of methylated nitrogenous DNA base guanine (m(9) Gua) with 1 to 6 molecules of anticancer drug ThioTEPA (1,1',1''-phosphorothioyltriaziridine) have been investigated by molecular modeling techniques (molecular docking and DFT geometry optimization), ab initio wavefunction calculations and the quantum theory of atoms in molecules (QTAIM). The accuracy of complex structures predicted by standard molecular docking techniques have been assessed by comparing them with ab initio calculations, and the most important differences have been discussed. Obtained stabilization enthalpies (kcal/mol) for the m(9) Gua⋅⋅⋅(ThioTEPA)n complexes with n=1…6 have been found to be -15.6, -26.5, -38.4, -49.6, -60.5 and -69.3 respectively. The non-covalent interactions revealed by the QTAIM method have been shown to be a dominating factor responsible for the complex stability, with hydrogen bonds of NH⋅⋅⋅N type being the most important interactions in small (n=1 to 4) and CH⋅⋅⋅N bonds - in large (n=5, 6) complexes. The obtained results may help to understand ThioTEPA-DNA interactions and clarify the mechanism of the drug action.

Characterization and in vivo evaluation of chitosan-hydroxyapatite bone scaffolds made by one step coprecipitation method.

Chitosan/hydroxyapatite scaffolds could be used for bone regeneration in case the application of auto- or allografts is impossible. The objective of the present work was to characterize and study in vivo biodegradation of simple chitosan/hydroxyapatite scaffolds. For this purpose, a series of chitosan/hydroxyapatite composites has been synthesized in aqueous medium from chitosan solution and soluble precursor salts by a one step coprecipitation method. A study of in vivo behavior of the materials was then performed using model linear rats. Cylindrical-shaped rods made of the chitosan/hydroxyapatite composite material were implanted into tibial bones of the rats. After 5, 10, 15, and 24 days of implantation, histological and histo-morphometric analyses of decalcified specimens were performed to evaluate the stages of biodegradation processes. Calcified specimens were examined by scanning electron microscopy with X-ray microanalysis to compare elemental composition and morphological characteristics of the implant and the bone during integration. Porous chitosan/hydroxyapatite scaffolds have shown osteoconductive properties and have been replaced in the in vivo experiments by newly formed bone tissue.