A micelle-like structure of poloxamer–methotrexate conjugates as nanocarrier for methotrexate delivery.

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 6–7 h) 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. [ABSTRACT FROM AUTHOR]