Репозиторий Университета

©2018 by the authors. Licensee MDPI, Basel, Switzerland. Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a “smart” drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge. These challenges can be overcome by using a study model that integrates the three-dimensional aspect of a tumour in a culture system. Here, we tested the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) to specifically target and penetrate the inner core of three-dimensional avascular human pancreatic and breast tumour spheroids in culture. The copolymer was quantitatively analyzed for its hydrophobic drug encapsulation efficiency using three different chemical drug structures with different molecular weights. Their release profiles and tumour targeting properties at various concentrations and pH environments were also characterized. Using the anticancer drug curcumin and two standard clinical chemotherapeutic hydrophobic drugs, paclitaxel and 5-fluorouracil, we tested the ability of FA-DABA-SMA nanoparticles to encapsulate the differently sized drugs and deliver them to kill monolayer pancreatic cancer cells using the WST-1 cell proliferation assay. The findings of this study revealed that the functionalized folic acid-conjugated amphiphilic alternating copolymer shows unique properties as an active “smart” tumor-targeting drug delivery system with the ability to internalize hydrophobic drugs and release the chemotherapeutics for effective killing of cancer cells. The novelty of the study is the first to demonstrate a functionalized “smart” drug delivery system encapsulated with a hydrophobic drug effectively targeting and penetrating the inner core of pancreatic and breast cancer spheroids and reducing their volumes in a dose-and time-dependent manner.

© Bionika Media Ltd. A systems analysis of the data available in the literature on the problem of choosing the optimal folate formulation in order to correct folate status in obstetric and gynecologic practice was carried out. There is plenty of evidence that increasing the folate status reduces the risk of neonatal neural tube defects. Higher folate intake through supplementation with folic acid (FA) or 5-methyltetrahydrofolate (L-methyl-THF) is recommended during pregravid preparation and early pregnancy. L-5-methyl-THF has a number of advantages over FA, since it is a physiological compound and has greater bioavailability. 5-methyl-THF is also available as a crystalline form of calcium salt (metafolin) that has the stability required for use as a supplement. When correcting the folate status in obstetric and gynecological practice, it is recommended that a choice should be made in favor of a formulation that has the best bioavailability, as seen in metafolin.

© 2018 Nutritec. All rights reserved. The results of assessing the sufficiency offolic acid of the residents of the Moscow region have been presented depending on rs1801133 MTHFRgene polymorphism and rs9939609 FTO gene polymorphism. A total of 326 people were examined, including 74 men and 252 women aged 20 to 65 years. The results of determining the level of folic acid in blood serum showed insufficiency of this vitamin among the population of the Moscow region of the Russian Federation. The expressed vitamin deficit (level <3,0 ng/ml) was detected in 24.2% of the surveyed residents, in 22.8% folic acid level was at the lower bound of the norm (3.0-4.5 ng/ml). The results of genotyping showed a statistically significant association of low folic acid level with rs1801133 MTHFR gene polymorphism in carriers of A allele of rs9939609 FTO gene polymorphism both in the homozygous state (genotype AA) and in the heterozygous (genotype AT) state, OR=4.26; CI (1.40-12.9), p=0.008, as well as with rs9939609 FTO gene polymorphism in carriers of the T allele of rs1801133 MTHFR gene polymorphism both in the homozygous (genotype TT) and heterozygous (CTgenotype) state, OR-3.29; CI (1.07-10.1), p=0.03. In carriers of 3 alleles of risk offolic acid deficiency [rs9939609 FTO gene polymorphism and rs1801133 MTHFR gene polymorphism (genotypes CT/AA and TT/AT)] blood serum level of folic acid was below the norm, that indicated folate deficiency in this category of persons.