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.