WATER-SOLUBLE POLYMERIC IONIC 5-FLUOROURACIL COMPLEX BASED ON METHACRYLIC ACID COPOLYMERS

Objective: The objective of this work was to obtain a water-soluble 5-fluorouracil (5-FU) polymeric complex on the basis of a methacrylic acid (MAA) copolymer to be used as an injectable chemotherapeutic agent. Methods: A polymeric carrier was synthesized using tert-butyl methacrylate (TBMA) as a monomer, thioglycolic acid, and azobisisobutyronitrile as a radical polymerization initiator. The polymer was converted by acid hydrolysis into a water-soluble copolymer of TBMA and MAA of 20: 80 mass%, respectively. The copolymer of TBMA and MAA was modified with 5-FU. Their formation was proved using IR and UV spectroscopy. The particle size of the 5-FU polymeric complex was estimated by turbidimetry, which is based on measuring the intensity of light transmitted through a disperse system. The release of 5-FU from the obtained ionic complexes by dialysis in vitro was evaluated. Results: Polymeric carriers were obtained with different amounts of 5-FU (5, 15, 25, 50 mol%). A high peak at λ = 266 nm was observed in the UV spectrum of the polymeric carrier (characteristic of 5-FU). The particle size was estimated at 13 nm for the complex with 5 mol% 5-FU and 26.8 n for the complex with 50 mol% 5-FU. The 5-FU release was estimated in two parallel experiments at 37 °C. One utilized a phosphate-citrate buffer with pH 5.0 to model the intracellular space and the other, a phosphate buffer with pH 7.4 to model the intravascular space. Two systems, with 5 and 15 mol% 5-FU, were chosen for testing. In both phosphate buffer and phosphate-citrate buffer, 5-FU was released from the polymeric complex with 5 mol% 5-FU approximately 1.3 times faster than from the complex containing 5 mol% 5-fluorouracil. The kinetics of 5-FU release from the polymeric complex (5 mol% 5-fluorouracil) showed that the 5-FU release was 77.9% in phosphate-citrate buffer and 59.6% in phosphate buffer over 52 h of dialysis. When the 5-FU release kinetics was studied with the polymeric complex containing 15 mol% 5-FU, the 5-FU release was 100.0% in phosphate-citrate buffer and 75.1% in phosphate buffer over 57 h of dialysis. Conclusion: Water-soluble nanoscale complexes of 5-FU with TBMA–MAA copolymers extend application of 5-FU, while its general toxicity might be lower. The complexes are sufficiently stable at pH 7.4 and readily release 5-FU at pH 5.0

Primary sclerosing holangitis in children with Crohn’s disease and ulcerative colitis

The article discusses the features of the course of ulcerative colitis and Crohn's disease in children. The authors have established the leading clinical and laboratory signs indicating the formation of primary sclerosing cholangitis in patients with inflammatory bowel diseaseВ статье рассмотрены особенности течения язвенного колита и болезни Крона у детей. Авторами установлены ведущие клинико-лабораторные признаки, указывающие на формирование первичного склерозирующего холангита у пациентов с воспалительным заболеванием кишечник

In vitro assessment of electrospun polyamide-6 scaffolds for esophageal tissue engineering

© 2018 Wiley Periodicals, Inc. Artificial tissue-engineered grafts offer a potential alternative to autologous tissue grafts for patients, which can be traumatic. After decellularizing Papio hamadryas esophagus and studying the morphology and physical properties of the extracellular matrix (ECM), we generated electrospun polyamide-6 based scaffolds to mimic it. The scaffolds supported a greater mechanical load than the native ECM and demonstrated similar 3D microstructure, with randomly aligned fibers, 90% porosity, 29 μm maximal pore size, and average fiber diameter of 2.87 ± 0.95 µm. Biocompatibility studies showed that human adipose- and bone marrow-derived mesenchymal stromal cells (AD-MSC and BMD-MSC) adhered to the scaffold surface and showed some proliferation: scaffold cell coverage was 25% after 72 h of incubation when seeded with 1000 cells/mm 2 ; cells elongated processes along the polyamide-6, although they flattened 1.67–4 times less than on cell culture plastic. Human umbilical vein endothelial cells, however, showed poor adherence and proliferation. We thus provide in vitro evidence that polyamide-6 scaffolds approximating the esophageal biomechanics and 3D topography of nonhuman primates may provide a biocompatible substrate for both AD-MSC and BMD-MSCs, supporting their adhesion and survival to some degree. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 253–268, 2019

In vitro assessment of electrospun polyamide-6 scaffolds for esophageal tissue engineering

© 2018 Wiley Periodicals, Inc. Artificial tissue-engineered grafts offer a potential alternative to autologous tissue grafts for patients, which can be traumatic. After decellularizing Papio hamadryas esophagus and studying the morphology and physical properties of the extracellular matrix (ECM), we generated electrospun polyamide-6 based scaffolds to mimic it. The scaffolds supported a greater mechanical load than the native ECM and demonstrated similar 3D microstructure, with randomly aligned fibers, 90% porosity, 29 μm maximal pore size, and average fiber diameter of 2.87 ± 0.95 µm. Biocompatibility studies showed that human adipose- and bone marrow-derived mesenchymal stromal cells (AD-MSC and BMD-MSC) adhered to the scaffold surface and showed some proliferation: scaffold cell coverage was 25% after 72 h of incubation when seeded with 1000 cells/mm 2 ; cells elongated processes along the polyamide-6, although they flattened 1.67–4 times less than on cell culture plastic. Human umbilical vein endothelial cells, however, showed poor adherence and proliferation. We thus provide in vitro evidence that polyamide-6 scaffolds approximating the esophageal biomechanics and 3D topography of nonhuman primates may provide a biocompatible substrate for both AD-MSC and BMD-MSCs, supporting their adhesion and survival to some degree. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 253–268, 2019