A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery.
Int J Pharm
; 487(1-2): 177-86, 2015 Jun 20.
Article
en En
| MEDLINE
| ID: mdl-25865570
ABSTRACT
The purpose of this study was to develop a novel featured and flexible methotrexate (MTX) formulation, in which MTX was physically entrapped and chemically conjugated in the same drug delivery system. A series of poloxamer-MTX (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through an ester bond. p-MTX conjugates could self-assemble into micelle-like structures in aqueous environment and the MTX end was in the inner-core of micelles. Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic core region to increase the total drug loading. Importantly, the resulting MTX-loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast release of the entrapped MTX (about 6-7h) followed by a sustained release of the conjugated MTX. The pharmacokinetics study showed that the mean residence time (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed MTX elimination from the bloodstream and prolonged in vivo residence time. Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p-MTX micelles might be a promising nanosized drug delivery system for the cancer therapy.
Palabras clave
Bioavailability; Biphasic release; Dicyclohexylcarbodiimide (PubChem CID: 10868); Dicyclohexylurea (PubChem CID: 4277); Dimethylaminopyridine (PubChem CID: 14284); MTX; Methanol (PubChem CID: 887); Methotrexate (PubChem CID: 24897373); Micelles; N,N-dimethylformamide (PubChem CID: 6228); N-hydroxysuccinimide (PubChem CID: 80170); Poloxamer; Poloxamer (PubChem CID: 10129990); Pyrene (PubChem CID: 31423); Theophylline (PubChem CID: 2153)
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metotrexato
/
Nanopartículas
/
Antimetabolitos
Límite:
Animals
Idioma:
En
Revista:
Int J Pharm
Año:
2015
Tipo del documento:
Article
País de afiliación:
China