RESUMEN
Liposomes represent one of the most extensively studied nano-carriers due to their potential in targeted drug delivery. However, the complex in vivo fate, particularly under pathological conditions, presents challenges for clinical translation of liposomal therapeutics. Liver serves as the most important organ for liposome accumulation and metabolism. Unfortunately, the fate of liposomes under pathological liver conditions has been significantly overlooked. This study aimed to investigate the in vivo pharmacokinetic profile and biodistribution profile of liposomes under drug-induced liver injury (DILI) conditions. Two classic DILI animal models, i.e. acetaminophen-induced acute liver injury (AILI) and triptolide-induced subacute liver injury (TILI), were established to observe the effect of pathological liver conditions on the in vivo performance of liposomes. The study revealed significant changes in the in vivo fate of liposomes following DILI, including prolonged blood circulation and enhanced hepatic accumulation of liposomes. Changes in the composition of plasma proteins and mononuclear phagocyte system (MPS)-related cell subpopulations collectively led to the altered in vivo fate of liposomes under liver injury conditions. Despite liver injury, macrophages remained the primary cells responsible for liposomes uptake in liver, with the recruited monocyte-derived macrophages exhibiting enhanced ability to phagocytose liposomes under pathological conditions. These findings indicated that high capture of liposomes by the recruited hepatic macrophages not only offered potential solutions for targeted delivery, but also warned the clinical application of patients under pathological liver conditions.
Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Diterpenos , Liposomas , Hígado , Fenantrenos , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Acetaminofén/farmacocinética , Ratones , Masculino , Hígado/metabolismo , Hígado/efectos de los fármacos , Distribución Tisular , Fenantrenos/farmacocinética , Fenantrenos/administración & dosificación , Fenantrenos/toxicidad , Diterpenos/farmacocinética , Diterpenos/administración & dosificación , Compuestos Epoxi/farmacocinética , Compuestos Epoxi/administración & dosificación , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos/métodos , Ratones Endogámicos C57BLRESUMEN
In recent years, filamentous algae blooms and microplastics (MPs) pollution have become two major ecological and environmental problems in urban water systems. In order to solve these two problems at the same time, this study explored the loading capacity of MPs on fresh filamentous algae, and successfully synthesized magnetic filamentous algae biochar loading with Fe3O4 by hydrothermal method, with the purpose of removing MPs from water. The magnetic filamentous algal biochar was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and so on. Experiments on adsorption kinetics, adsorption isotherms and optimum pH were carried out to explore the adsorption mechanism of MPs on magnetic filamentous algal biochar. The adsorption kinetics and adsorption isotherm models were evaluated, and the selection criterion for the appropriate model was determined by using the residual sum of squares (RSS) and Bayesian information criterion (BIC). Microscope images revealed that fresh filamentous algae could interact with MPs in the form of entanglement, adhesion and encapsulation. The average load of MPs in filamentous algae samples was 14.1 ± 5 items/g dry weight. The theoretical maximum adsorption capacities of polystyrene MPs (PS-MPs) by raw biochar (A500) and magnetic biochar with Fe3O4 (M2A500) were 176.99 mg/g and 215.58 mg/g, respectively. The adsorbent materials gave better reusability because they could be reused up to five times. Overall, these findings have provided new insights into the use of filamentous algae for in situ remediation of fluvial MPs pollution, as well as feasible strategies for the recycling of algal waste.
Asunto(s)
Carbón Orgánico , Microplásticos , Contaminantes Químicos del Agua , Carbón Orgánico/química , Adsorción , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , CinéticaRESUMEN
With the increasing requirement of environmental protection, the development of lubricating materials with non-toxicity and good biodegradability becomes more and more significant. As the novel green nanomaterial derived from natural cellulose, cellulose nanocrystals (CNCs) in the present work were prepared from native cotton and added into polyalphaolefin (PAO) base oil as the lubricant additive. To improve the compatibility of CNCs with PAO, the surface of CNCs were grafted by stearoyl chains, which entangled with polyolefin chains and led to a good dispersibility and stability of the colloidal solution. This hybrid oil with the elevated viscosity improved the formation of lubricant film in the boundary lubrication regime. Combining with the mending effect of CNC particles on the surface roughness and scars, both the friction and the wear were dramatically reduced. Specifically, the introduction of 2 wt% modified nanocrystals (mCNC) in PAO base oil reduced the coefficient of friction (COF) by 30%. The results of this study suggest that cellulose nanocrystal is a promising ecofriendly and effective lubricant additive.
Asunto(s)
Alquenos/química , Celulosa/química , Gossypium/metabolismo , Lubricantes/química , Nanopartículas/química , Fricción , Lubrificación , Propiedades de Superficie , ViscosidadRESUMEN
Enterovirus 71 (EV71), a member of Picornaviridae, is one of the major pathogens of human hand, foot and mouth disease. EV71 mainly infects children and causes severe neurological complications and even death. The pathogenesis of EV71 infection is largely unknown, and no clinically approved vaccine or effective treatment is available to date. Here we described a novel bioluminescence imaging approach for EV71 detection. In this approach, a plasmid-based reporter was constructed to express the fusion protein AmN(Q/G)BC, a split firefly luciferase mutant, which can be specifically cleaved by EV71 protease 3C(pro). Upon cleavage, the splitting fusion protein restores luciferase activity. Our test confirmed that AmN(Q/G)BC was specifically cleaved by 3C(pro) and EV71 and restored the luciferase activity to a degree that corresponds to the 3C(pro) and virus doses in cells and mice. The anti-EV71 effect of GW5074 and U0126, two mitogen-activated protein kinase (MAPK) inhibitors, was evaluated using this approach to validate its application of screening anti-EV71 agents. We found that the AmN(Q/G)BC reporter efficiently monitored the inhibitory effect of GW5074 and U0126 on EV71 infection under in vitro and in vivo conditions. The data from AmN(Q/G)BC reporter were consistent with Western blotting and histopathology examination. Taken together, this real-time imaging approach can quantitatively monitor the efficacy of anti-EV71 agents and is valuable for anti-EV71 drug screening and evaluation, especially, under in vivo conditions.