Magdalena Peruzynska

CYP3A5 and CYP3A4, but not ABCB1 polymorphisms affect tacrolimus dose-adjusted trough concentrations in kidney transplant recipients

BACKGROUND Tacrolimus (TAC), acting as a calcineurin inhibitor, is an immunosuppressant widely used after kidney transplantation. TAC requires blood concentration monitoring due to large interindividual variability in its pharmacokinetics and a narrow therapeutic index. Since genetic factors are considered responsible for a part of the observed pharmacokinetic variability, hereby SNPs within the CYP3A4, CYP3A5 and ABCB1 genes in kidney transplant patients of Polish Caucasian origin were investigated. PATIENTS & METHODS A total of 241 patients treated with TAC through the first year after kidney transplantation were genotyped for the presence of common SNPs: rs776746:A>G (CYP3A5*3), rs35599367:C>T (CYP3A4*22), rs2740574:A>G (CYP3A4*1B) and rs1045642:C>T (ABCB1 3435C>T) using TaqMan(®) assays. RESULTS CYP3A5 expressers received significantly higher weight-adjusted TAC doses, and were characterized by markedly lower C0 and dose adjusted C0 values in the course of treatment. CYP3A4*1B was significantly associated with TAC pharmacokinetics in univariate analysis. Impact of the CYP3A4*22 allele was significant only at particular time points, that is, 3 months after transplantation, with marginal significance 6 months after transplantation. The ABCB1 genotype did not influence TAC pharmacokinetics. Multivariate analysis of all the studied loci demonstrated that only the CYP3A5*1 (starting from month 1) and CYP3A4*22 alleles (at 3 and 6 months) were independent predictors of TAC dose-adjusted C0. CONCLUSION Our results confirm the impact of the CYP3A4*22 allele on TAC pharmacokinetics, as a second significant genetic factor (in addition to the CYP3A5*1 allele) influencing TAC dose-adjusted blood concentrations in kidney transplant recipients.

Mesoporous Silica Nanospheres Functionalized by Tio2 as a Photoactive Antibacterial Agent

In this contribution we present comparative study on synthesis, bio-characterization and antibacterial properties of mesoporous silica nanospheres modified by titanium dioxide. Mesoporous silica nanospheres functionalized by titania were studied as light activated antibacterial agents. The analysis of the antibacterial effects on E. coli ATCC 25922 shows strong enhancement during the visible and ultraviolet light irradiation in respect to the commercial catalyst and sample free from the nanomaterials. In darkness the mesoporous silica/titania nanostructures revealed low antibacterial activity dependent on the stirring intensity of the suspension containing nanomaterials and bacteria. The nanomaterials toxicity was determined on the amount of lactate dehydrogenase released from mouse fibroblast cells L929 with LDH assay. Sample was characterized in details by means of high resolution transmission electron microscopy (HR-TEM), Raman spectroscopy, XRD and BET Isotherm.

Antibacterial performance of nanocrystallined titania confined in mesoporous silica nanotubes

In this paper, we study synthesis and characteristics of mesoporous silica nanotubes modified by titanium dioxide, as well as their antimicrobial properties and influence on mitochondrial activity of mouse fibroblast L929. Nanocrystalized titania is confined in mesopores of silica nanotubes and its light activated antibacterial response is revealed. The analysis of the antibacterial effect on Escherichia coli. (ATCC 25922) shows strong enhancement during irradiation with the artificial visible and ultraviolet light in respect to the commercial catalyst and control sample free from the nanomaterials. In darkness, the mesoporous silica/titania nanostructures exhibited antibacterial activity dependent on the stirring speed of the suspension containing nanomaterials. Obtained micrograph proved internalization of the sample into the microorganism trough the cell membrane. The analysis of the mitochondrial activity and amount of lactate dehydrogenase released from mouse fibroblast cells L929 in the presence of the sample were determined with LDH and WST1 assays, respectively. The synthesized silica/titania antibacterial agent also exhibits pronounced photoinduced inactivation of the bacterial growth under the artificial visible and UV light irritation in respect to the commercial catalyst. Additionally, mesoporous silica/titania nanotubes were characterized in details by means of high resolution transmission electron microscopy (HR-TEM), XRD and BET Isotherm.

Study on size effect of the silica nanospheres with solid core and mesoporous shell on cellular uptake.

The properties of mesoporous silica nanoparticles including large surface area, large pore volume, easy surface functionalization and control of structure and pore size has made them promising drug carriers. In this study, the effect of different diameters (50 nm, 70 nm, 90 nm, 110 nm and 140 nm) of silica nanospheres with a solid core and mesoporous shell (mSiO2/SiO2) on cellular internalization in mouse fibroblast cells (L929) was evaluated. The physical properties of the nanostructures were characterized with various methods, such as transmission electron microscopy with x-ray dispersion spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy and zeta potential. In order to define the cellular uptake, the nanostructures were labelled with fluorescent dye Alexa647, and imaging and quantitative methods were applied: laser scanning confocal microscopy, flow cytometry and thermogravimetry. Our results indicate that cellular uptake of the studied nanospheres is size-dependent, and nanospheres of 90 nm in diameter showed the most efficient cell internalization. Thus, particle size is an important parameter that determines cellular uptake of nanoparticles and should be considered in designing drug delivery carriers.