RESUMO
We report biodegradable thermoplastic polyurethanes for soft tissue engineering applications, where frequently used carboxylic acid ester degradation motifs were substituted with carbonate moieties to achieve superior degradation properties. While the use of carbonates in soft blocks has been reported, their use in hard blocks of thermoplastic polyurethanes is unprecedented. Soft blocks consist of poly(hexamethylene carbonate), and hard blocks combine hexamethylene diisocyanate with the newly synthesized cleavable carbonate chain extender bis(3-hydroxypropylene)carbonate (BHPC), mimicking the motif of poly(trimethylene carbonate) with highly regarded degradation properties. Simultaneously, the mechanical benefits of segmented polyurethanes are exploited. A lower hard block concentration in BHPC-based polymers was more suitable for vascular grafts. Nonacidic degradation products and hard block dependent degradation rates were found. Implantation of BHPC-based electrospun degradable vascular prostheses in a small animal model revealed high patency rates and no signs of aneurysm formations. Specific vascular graft remodeling and only minimal signs of inflammatory reactions were observed.
Assuntos
Materiais Biocompatíveis/química , Prótese Vascular , Cimento de Policarboxilato/química , Poliuretanos/química , Animais , Aorta/patologia , Aorta/cirurgia , Fenômenos Biomecânicos , Isocianatos/química , Espectroscopia de Ressonância Magnética , Teste de Materiais , Microscopia Eletrônica de Varredura , Implantação de Prótese , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Typical bimolecular photoinitiators (PIs) for radical polymerization of acrylates show only poor photoreactivity because of the undesired effect of back electron transfer. To overcome this limitation, PIs consisting of a benzaldoxime ester and various sensitizers based on aromatic ketones were introduced. The core of the photoinduced reactivity was established by laser flash photolysis, photo-CIDNP, and EPR experiments at short time scales. According to these results, the primarily formed iminyl radicals are not particularly active. The polymerization is predominantly initiated by C-centered radicals. Photo-DSC experiments show reactivities comparable to that of classical monomolecular type I PIs like Darocur 1173.
RESUMO
Novel derivatives of the clinically established anticancer drug oxaliplatin were synthesized. Cytotoxicity of the compounds was studied in six human cancer cell lines by means of the MTT assay. Additionally, most promising complexes were also investigated in cisplatin- and oxaliplatin-resistant human cancer cell models. The therapeutic efficacy in vivo was studied in the murine L1210 leukemia model. Most remarkably, {(1R,2R,4R)-4-methyl-1,2-cyclohexanediamine}oxalatoplatinum(II), comprising an equatorial methyl substituent at position 4 of the cyclohexane ring, was as potent as oxaliplatin in vitro but distinctly more effective in the L1210 model in vivo at the optimal dose. The advantage observed in the in vivo situation was mainly based on a more favorable therapeutic index. The maximum tolerated dose of the novel analogue was higher than that of oxaliplatin and caused a greater increase in life span (>200% versus 152%), with more animals experiencing long-term survival (5/6 versus 2/6). These data support further (pre)clinical development of the methyl-substituted oxaliplatin analogue with improved anticancer activity.