RESUMEN
Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease that seriously threatens human life and health. Our previous study demonstrated the unique superiority of traditional Chinese medicine cryptotanshinone (CTS) combined with sustained pulmonary drug delivery for treating PF. In this study, we aimed to enhance the selectivity, targeting efficiency and sustained-release capability based on this delivery system. To this end, we developed and evaluated CTS-loaded modified liposomes-chitosan (CS) microspheres SM(CT-lipo) and liposome-exosome hybrid bionic vesicles-CS microspheres SM(LE). The prepared nano-in-micro particles system integrates the advantages of the carriers and complements each other. SM(CT-lipo) and SM(LE) achieved lung myofibroblast-specific targeting through CREKA peptide binding specifically to fibronectin (FN) and the homing effect of exosomes on parent cells, respectively, facilitating efficient delivery of anti-fibrosis drugs to lung lesions. Furthermore, compared with daily administration of conventional microspheres SM(NC) and positive control drug pirfenidone (PFD), inhaled administration of SM(CT-lipo) and SM(LE) every two days still attained similar efficacy, exhibiting excellent sustained drug release ability. In summary, our findings suggest that the developed SM(CT-lipo) and SM(LE) delivery strategies could achieve more accurate, efficient and safe therapy, providing novel insights into the treatment of chronic PF.
Asunto(s)
Quitosano , Exosomas , Fibronectinas , Liposomas , Fibrosis Pulmonar , Animales , Humanos , Masculino , Administración por Inhalación , Antifibróticos/administración & dosificación , Antifibróticos/química , Quitosano/química , Quitosano/administración & dosificación , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Exosomas/química , Fibronectinas/administración & dosificación , Liposomas/química , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Microesferas , Fenantrenos/administración & dosificación , Fenantrenos/química , Fenantrenos/farmacocinética , Fibrosis Pulmonar/tratamiento farmacológico , Piridonas , Ratas Sprague-Dawley , RatasRESUMEN
Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (nâ¯=â¯10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7â¯days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (pâ¯<â¯0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (pâ¯<â¯0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (pâ¯<â¯0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism.
Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Metabolismo Energético , Fibronectinas/administración & dosificación , Hormonas Tiroideas/metabolismo , Animales , Ingestión de Alimentos , Fibronectinas/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Masculino , ARN Mensajero/metabolismo , Ratas Wistar , Tiroxina/sangre , Triyodotironina/sangre , Proteína Desacopladora 1 , Proteína Desacopladora 3/metabolismoRESUMEN
A wide range of biochemical signals promoting cell functions (adhesion, migration, proliferation, and differentiation) and thereby improving the osseointegration process are currently investigated. Unfortunately, their application for the production of bioactive implantable devices is often hampered by their insolubility; instability; and limited availability of a large amount of inexpensive, high-purity samples. An attractive alternative is the use of short peptides carrying the minimum active sequence of the natural factors. Synthetic peptides mapped on fibronectin and vitronectin have been demonstrated to enhance cell adhesion both to polystyrene and acellular bone matrix; in particular, a nonapeptide sequence from human vitronectin works via an osteoblast-specific adhesion mechanism. In this study, we incorporated these peptides into a sol-gel silica dressing applied to coat sand-blasted and acid-attacked titanium samples; measured the kinetic of peptide release; and used titanium disks, coated with a peptide-enriched film, as substrates to determine the peptide concentration that maximizes cell adhesion in vitro. We also evaluated in vivo the capacity of the vitronectin-derived peptide to improve osteogenic activity: histologic analysis revealed markedly improved osteogenic activity around peptide-enriched samples. This article also discusses the role of surface characteristics and the importance of bioactive peptides.