The role of stabilizers and mechanical processes on physico-chemical and anti-inflammatory properties of methotrexate nanosuspensions

The aim of this study was to investigate two different mechanical processes (Ultra-turrax® and Sonication) and two stabilizers (Methyl cellulose (MC) and Poloxamer 407 (P407)) on the physico-chemical and anti-inflammatory properties of the MTX nanosuspensions. The mechanical process, presence and ty...

Descripción completa

Detalles Bibliográficos
Autores: Santos, Aline Martins dos [UNESP], Meneguin, Andréia Bagliotti [UNESP], Fonseca-Santos, Bruno [UNESP], Chaves de Souza, Maurício Palmeira [UNESP], Barboza Ferreira, Leonardo Miziara [UNESP], Sábio, Rafael Miguel [UNESP], Chorilli, Marlus [UNESP], Daflon Gremião, Maria Palmira [UNESP]
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:Brasil
Institución:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/201629
Acceso en línea:http://dx.doi.org/10.1016/j.jddst.2020.101638
http://hdl.handle.net/11449/201629
Access Level:acceso abierto
Palabra clave:Acid-base neutralization
Anti-inflammatory activity
Bottom-up process
Methotrexate
Methyl cellulose
Nanosuspension
Poloxamer 407
Descripción
Sumario:The aim of this study was to investigate two different mechanical processes (Ultra-turrax® and Sonication) and two stabilizers (Methyl cellulose (MC) and Poloxamer 407 (P407)) on the physico-chemical and anti-inflammatory properties of the MTX nanosuspensions. The mechanical process, presence and type of stabilizers showed a strong impact on the particle size, polydispersity index (PDI), zeta potential and morphology of MTX nanosuspensions. In particular, the surfactant property of P407 in combination sonication process reduced significantly the particle size of MTX to nano-range size. Short term stability evaluated by dynamic light scattering (DLS) technique proved that the addition of the stabilizers MC and P407 on the MTX nanosuspensions provided stability through of the steric hindrance. In vitro dissolution studies showed that MTX nanosuspensions enhanced the drug release rates, revealing the influence of the different particle size on the drug release profiles. In vivo inflammation study indicated that MTX nanosuspensions presented a greater effect on the anti-inflammatory activity, maintaining this effect for up to 6 h, being more effective than the positive control. It could be concluded that the combined usage of mechanical processes and stabilizers modified in vitro and in vivo performance of the MTX nanosuspensions. Therefore, these results confirm the potential of these nanosuspensions as a promising tool for enhancement of dissolution rate and oral bioavailability of poorly water-soluble drugs, such as MTX.