RESUMEN
Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.
Asunto(s)
Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Metilprednisolona/administración & dosificación , Metilprednisolona/farmacología , Proteína A Asociada a Surfactante Pulmonar/administración & dosificación , Proteína A Asociada a Surfactante Pulmonar/farmacología , Animales , Química Farmacéutica , Portadores de Fármacos/química , Ensayo de Inmunoadsorción Enzimática , Humanos , Liposomas/química , Pulmón/efectos de los fármacos , Masculino , Ratones , Ratones Desnudos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Anticuerpos de Dominio Único/administración & dosificación , Anticuerpos de Dominio Único/farmacologíaRESUMEN
The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-ß1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Liposomas/química , Metilprednisolona/química , Metilprednisolona/farmacología , Nanopartículas/química , Proteína A Asociada a Surfactante Pulmonar/química , Animales , Líquido del Lavado Bronquioalveolar/química , Sistemas de Liberación de Medicamentos/métodos , Glucocorticoides/química , Glucocorticoides/farmacología , Interleucina-8/metabolismo , Pulmón/efectos de los fármacos , Masculino , Surfactantes Pulmonares/química , Surfactantes Pulmonares/farmacología , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To evaluate the marginal adaptation between the new nano-hydroxyapatite composite resin and tooth. METHODS: Thirty extracted healthy premolars were randomly assigned to three groups according to the material employed: New nano-hydroxyapatite composite resin (Group A), Karisma composite resin (Group B), and glass ionomer cement (Group C). After the thermal cycling, the teeth were immersed in 2% methylene blue dye, and the depth of microleakage between the composite and tooth structure were observed. RESULTS: The microleakage depth of group A, B and C were (1.20+/-0.81), (1.94+/-0.70), and (1.73+/-0.54) mm, respectively. No statistically significant differences were found among the three groups (P>0.05). There was no significant difference in the degree of microleakage (P>0.05). CONCLUSION: As a new dental restorative material, new nano-hydroxyapatite composite resin has good bonding performance to the tooth structure.
Asunto(s)
Filtración Dental , Cementos de Resina , Resinas Compuestas , Restauración Dental Permanente , Durapatita , Cementos de Ionómero Vítreo , HumanosRESUMEN
PURPOSE: To evaluate the shear bond strength and bonding ability between the new nano-hydroxyapatite composite resin and tooth structure. METHODS: Thirty-six healthy isolated molars were randomly assigned to 3 groups according to the material employed: new nano-hydroxyapatite composite resin, composite resin karisma and glass ionomer cement. After thermal cycling, the data of shear bond strength was recorded, and the type of specimen fracture section was observed under stereo microscope. The data was analyzed statistically by SPSS17.0 software package. RESULTS: The average shear bonding strength of nano-hydroxyapatite composite resin was (11.23±4.6082) N/mm(2), and that of composite resin charisma and glass ionomer cement was (14.49±7.9855) N/mm(2) and(10.08±6.3701) N/mm(2), respectively. No significant difference was found among 3 groups. The bonding fracture mode of each specimen had no significant difference(P>0.05). CONCLUSIONS: As a new dental restorative material, new nano-hydroxyapatite composite resin has superior bonding ability and can be used in clinical therapy. Supported by Natural Science Foundation of Shandong Province (Y2008C159).