The structure, the stress-strain state, and the mechanical properties (hardness and wear resistance) of titanium nitride coatings deposited on a substrate by a vacuum-arc method at constant (from -5 V to -230 V) and high-frequency pulse (-1000 V) negative potentials are studied. The laws of formation of the coatings are determined. The formed coatings are analyzed using a model of two-level action of the implanted ions on them.

Both favorable pregnancy outcomes and fetal abnormalities have been associated with the use of tyrosine kinase inhibitors (TKIs) during pregnancy. The placental transfer of TKIs in humans is poorly understood. We observed women with chronic myeloid leukemia who used imatinib or nilotinib during the late pregnancy stages. The newborns had no birth abnormalities. We evaluated the drug concentrations in maternal blood, umbilical cord blood, and placental samples collected during labor. We found limited placental transfer of the TKIs. The fetal/maternal concentration ratio ranged from 0.5 to 0.58 for nilotinib and from 0.05 to 0.22 for imatinib. The placental/maternal ratio was higher for imatinib than for nilotinib. Theoretical pharmacokinetic modeling of passive placental crossing was insufficient to predict the in vivo data because the calculated fetal/maternal ratio was close to 1 for both drugs. We propose that active placental transport contributes to fetal protection against TKI exposure during pregnancy.

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Breastfeeding in patients with chronic myeloid leukaemia (CML) during tyrosine kinase inhibitors (TKIs) therapy is not recommended but interruption of TKI treatment may cause the loss of remission. We studied the 3 cases of pregnancy and breastfeeding in women with CML and observed that stopping treatment without major molecular response may end in haematological relapse. The concentrations of nilotinib and imatinib in maternal milk were measured and nilotinib distribution in human breast milk was demonstrated for the first time. The estimated maximal doses of imatinib and nilotinib which an infant may ingest with the maternal milk were less than the therapeutical doses. However, the unknown impact of the low dose chronic exposure to these TKIs in infants imposes the limitations on their use during breastfeeding. Breastfeeding without TKI treatment may be safe with molecular monitoring, but preferably in those patients with CML who have durable deep molecular response.

Background: Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible polymer which is widely used as a matrix to incorporate therapeutic agents. The anticancer activity of targeted folate-modified docetaxel-loaded PLGA nanoparticles (F-NP-Doc) was studied in vitro. Methods: Nanoparticles were prepared by a single-emulsion solvent-evaporation technique and characterized by physico-chemical methods. Cell survival was measured by the MTT assay and the sulforhodamine B assay. Folate receptor α expression, particle uptake and apoptosis were assessed by flow cytometry. Results: Folate-modified docetaxel-loaded PLGA nanoparticles showed high anticancer activity in vitro against HeLa cervical carcinoma cells and MCF7 breast adenocarcinoma cells overexpressing folate receptors. Targeted F-NP-Doc nanoparticles were more active compared to free docetaxel and non-targeted NP-Doc nanoparticles; in contrast, the activity of targeted nanoparticles against human fibroblasts (negative control) was significantly lower. F-NP-Doc particles, like free docetaxel, induced apoptosis in cancer cells. F-NP-Doc, but not unmodified docetaxel-loaded PLGA nanoparticles, reversed multidrug resistance of MCF7 R breast adenocarcinoma cells. High antitumor activity of F-NP-Doc has also been proven in in vivo experiments. Conclusions: The summarized experimental data brought us to the conclusion that the incorporation of docetaxel into the targeted PLGA nanoparticles dramatically improves its selectivity against cancer cells.