RESUMEN
BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of severe visual deficits and blindness. Meanwhile, there is convincing evidence implicating oxidative stress, inflammation, and neovascularization in the onset and progression of AMD. Several studies have identified berberine hydrochloride and chrysophanol as potential treatments for ocular diseases based on their antioxidative, antiangiogenic, and anti-inflammatory effects. Unfortunately, their poor stability and bioavailability have limited their application. In order to overcome these disadvantages, we prepared a compound liposome system that can entrap these drugs simultaneously using the third polyamidoamine dendrimer (PAMAM G3.0) as a carrier. RESULTS: PAMAM G3.0-coated compound liposomes exhibited appreciable cellular permeability in human corneal epithelial cells and enhanced bio-adhesion on rabbit corneal epithelium. Moreover, coated liposomes greatly improved BBH bioavailability. Further, coated liposomes exhibited obviously protective effects in human retinal pigment epithelial cells and rat retinas after photooxidative retinal injury. Finally, administration of P-CBLs showed no sign of side effects on ocular surface structure in rabbits model. CONCLUSIONS: The PAMAM G3.0-liposome system thus displayed a potential use for treating various ocular diseases.
Asunto(s)
Antioxidantes/farmacocinética , Dendrímeros/química , Ojo/efectos de los fármacos , Liposomas/química , Poliaminas/química , Administración Oftálmica , Animales , Antioxidantes/administración & dosificación , Antioxidantes/efectos adversos , Transporte Biológico , Línea Celular , Córnea/citología , Liberación de Fármacos , Células Epiteliales/efectos de los fármacos , Fluoresceína-5-Isotiocianato/química , Colorantes Fluorescentes/química , Humanos , Liposomas/administración & dosificación , Liposomas/efectos adversos , Masculino , Imagen Óptica/métodos , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Conejos , Ratas , Ratas Sprague-Dawley , Propiedades de SuperficieRESUMEN
The use of plastic film mulch threatens the sustainability of the terrestrial environment because of the persistence of plastic residue. Identification of the potential long-term impacts of polyethylene (PE) residue on the soil microbiome has been overlooked in most studies. A long-term field experiment was conducted to expand this understanding by performing a co-occurrence network analysis of bacterial communities among different compartment niches (i.e. plastisphere, rhizosphere, and bulk soil) and three PE residue concentrations to determine the differential operational taxonomic units (OTUs) and keystone taxa. The specific set of bacterial microbes in the plastisphere was different from that of bulk soil and rhizosphere (R2 = 0.372, P < 0.001, PERMANOVA). Totally, 215 and 257 differential OTUs were identified in response to the different compartment niches and PE residue concentrations, respectively. Among these, several hubs or keystone taxa responsible for the exposure to PE residues were further identified, most of which have potential biodegradation functions. Exposure to PE residues led to a reduced network complexity and microbiome stability in the soil ecosystem. This study provides a comprehensive evidence on the alteration of bacterial communities and co-occurrence networks in the terrestrial environment as a legacy effect when exposed to PE residues, and has potential implications for predicting the ecological functions of the soil ecosystem.
Asunto(s)
Microbiota , Polietileno , Bacterias/genética , Rizosfera , Suelo , Microbiología del SueloRESUMEN
One of the main issues faced by nervous system diseases is that drugs are difficult to enter the brain. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study concentrated on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. Middle cerebral artery occlusion-reperfusion induced CIRI model rats to explore the protective effect of CVBD brain-targeted liposome on CIRI. Moreover, the protective effect of CVBD liposomes on OGD/R-injured HT22 cells was examined by cell fusion degree, cell proliferation curve and cell viability. OGD/R-injured HT22 cell was infected by mRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were observed by laser confocal microscopy, and autophagy-related protein expressions were analyzed by Western blot. The classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulatedmechanism of CVBD brain-targeted liposomes in treating CIRI. CVBD liposomes increased cell viability and decreased ROS level, improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated with anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro.
Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Animales , Antioxidantes/farmacología , Apoptosis , Autofagia , Encéfalo , Isquemia Encefálica/tratamiento farmacológico , Cloroquina/farmacología , Cloroquina/uso terapéutico , Medicamentos Herbarios Chinos , Liposomas/farmacología , Ratas , Especies Reactivas de Oxígeno , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & controlRESUMEN
The blood-brain barrier (BBB) poses a challenge for the treatment of cerebrovascular diseases including cerebral ischemia-reperfusion injury, Parkinson's syndrome, and cerebral tumors. Nanotechnology has developed as a promising strategy for drug delivery applications to the brain, especially liposomes (Lps) that have shown an intrinsic ability to cross the BBB. Angiopep-2 (ANG), a ligand for low-density lipoprotein receptor-related protein-1 (LRP1), is a good prospect for use as a targeting ligand for brain delivery using Lps. It was also reported that Polysorbate 80 (Tween 80, T80) plays a special role in brain targeting. Moreover, the nasal drug delivery method has attracted increased attention with its brain targeting capability in the clinical treatment of cerebrovascular diseases. The aim of this work was to evaluate the capability of Angiopep-conjugated Polysorbate 80-Coated Liposomes in the delivery of cyclovirobuxine D across the BBB in vitro and in vivo. For this purpose, we first synthesized DSPE-PEG2000-Angiopep-2 then cyclovirobuxine D was encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes (T80-An2-CVB-D-Lps) prepared by thin film evaporation and an ultrasonic technique. Formulations were characterized in terms of encapsulation efficiency, transmission electron microscope (TEM) morphology, size distribution, and zeta potential. Angiopep-conjugated Polysorbate 80-Coated Liposomes enhanced in vitro BBB transport of CVB-D compared to the nontargeted liposomes and the CVB-D solution in the BBB model consisting of brain microvascular endothelial (bEnd.3) cells. To evaluate the brain targeting of T80-An2-CVB-D-Lps in vivo, microdialysis samples were collected from the striatum and blood simultaneously. Rats were dosed with brain-targeting liposomes, CVB-D liposomes and CVB-D solution by intranasal administration and with brain-targeting liposomes by intravenous injection. The results showed that T80-An2-CVB-D-Lps were spherical, small (approximately 80 nm), homogeneously dispersed, negatively charged and possessed a high encapsulation efficiency. T80-An2-CVB-D-Lps crossed the BBB model better than the other treatments did. In addition, in a pharmacodynamic study, there was a higher AUC in the brain after T80-An2-CVB-D-Lps by intranasal administration. In conclusion, T80-An2-Lps can enhance the BBB permeability and improve the transport of CVB-D to the brain. This coadministration strategy can be utilized to enhance the brain accumulation in other cerebrovascular diseases.