RESUMO
Myocardial ischemia/reperfusion (MI/R) injury is an unresolved clinical challenge. The blockade of binding fibrinogen by glycoprotein IIb/IIIa (GPIIb-IIIa) inhibitors has become a new therapeutic approach against MI/R injury. In this study, we modified the RGD structure to combine with scutellarin and synthesized a novel peptide, scutellarin-HomoArg-Gly-Asp-Trp-NH2 (WK001). Herein, reported experimental and docking evidence indicates that WK001 provides immediate and potent platelet inhibition, with stronger inhibition of platelet aggregation than eptifibatide and scutellarin. In particular, it is administered intravenously to prevent thrombus formation and attenuate myocardial fibrosis progression in vivo. Therefore, WK001 could be developed as an antiplatelet drug to treat thrombosis-associated diseases, such as stroke and myocardial infarction.
Assuntos
Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Glicoproteínas da Membrana de Plaquetas , OligopeptídeosRESUMO
Biodegradable four-arm star-shaped poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (sPEG-b-PLLA), four-arm star-shaped poly(L-lactic acid) (sPLLA), linearly poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (PEG-b-PLLA) and linearly poly(L-lactic acid) (PLLA) were synthesized from L-lactice acid, pentaerythritol, poly(ethylene glycol) and star-shaped poly(ethylene glycol), using the method of melt polycondensation, and the products were characterized and confirmed by 1H NMR spectroscopy, FT-IR and GPC. Four types of ibuprofen loaded microspheres based on the above four types of polymers, i.e., IBU/PLLA, IBU/sPLLA, IBU/PEG-b-PLLA, and IBU/sPEG-b-PLLA microspheres were prepared using the method of solvent evaporation, and the optimized preparation technology was obtained via orthogonal experiments, and the drug-encapsulating properties and in vitro drug-releasing properties were studied. The results showed that compared with IBU/PLLA and IBU/PEG-b-PLLA microspheres, the drug encapsulate efficiency of IBU/sPLLA and IBU/sPEG-b-PLLA microspheres were higher and the in vitro drug releasing rate slowed down, which mainly due to the faster degradation of sPLLA and sPEG-b-PLLA for the star-shaped structure and the block copolymerization of sPEG. The drug releasing curves of these three types of microspheres could be fit by first-order equation, and the releasing mechanism was non-Fickian diffusing, i.e., the synergetic effect of polymer degradation and drug diffusion.
Assuntos
Portadores de Fármacos , Ibuprofeno/administração & dosagem , Polímeros/química , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Preparações de Ação Retardada , Ibuprofeno/química , Lactatos/química , Ácido Láctico/química , Espectroscopia de Ressonância Magnética , Microesferas , Tamanho da Partícula , Poliésteres , Polietilenoglicóis/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The increasing drug resistance of phytopathogenic bacteria to conventional bactericides has driven the necessity for exploring new alternatives with a lower tendency to develop bacterial resistance. Here, we report a novel cationic symmetrical peptide P5VP5 (Ac- R+ LI R+ K+ V K+ R+ IL R+ -NH2 that enables self-assembly to form nanoparticles with excellent thermal stability. An in vitro assay showed that P5VP5 nanoparticles exhibited excellent antibacterial activity against Xanthomonas axonopodis pv citri with a MIC value of 20 µM. Meanwhile, under an in planta condition, treatment with peptide nanoparticles demonstrated the highest ability to reduce the development of citrus canker lesions in leaves. Moreover, the nanoparticles could destroy the biofilm formation, damage the cell membranes, and affect the cell membrane permeability, ultimately leading to the death of bacteria. Taken together, these nanoparticles are a promising antibacterial agent that can be used to control citrus canker and other plant diseases caused by bacteria.