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

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.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Ren J,Fang Z,Yao L,Dahmani FZ,Yin L,Zhou J,Yao J

doi

10.1016/j.ijpharm.2015.04.014

subject

Has Abstract

pub_date

2015-06-20 00:00:00

pages

177-86

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(15)00322-1

journal_volume

487

pub_type

杂志文章

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