Iminoboronate-based dual-responsive micelles via
subcomponent self-assembly for hydrophilic 1,2-diol-containing drug delivery
Ma, RJ (Ma, Rujiang)[ 1,2 ] ; Zhang, C (Zhang, Chuan)[ 1 ] ; Liu, Y (Liu, Yong)[ 1 ] ; Li, C (Li, Chang)[ 1 ] ; Xu, YL (Xu, Yanling)[ 3 ] ; Li, BX (Li, Baoxin)[ 4 ] ; Zhang, YL (Zhang, Yunliang)[ 4 ] ; An, YL (An, Yingli)[ 1 ] ; Shi, LQ (Shi, Linqi)[ 1,2 ]
RSC ADVANCES,
2017, 7(34): 21328-21335
DOI: 10.1039/c7ra01742a
WOS:000399722300072
Abstract
Amphiphilic block copolymer micelles in aqueous solution
have been used extensively in delivery of hydrophobic drugs with the
hydrophobic core serving as the reservoir. However, encapsulation of
hydrophilic drugs by polymeric micelles with hydrophobic core is relatively
difficult because of the poor interaction between them. Herein, we report a
novel kind of pH/GSH dual-responsive complex micelles with a hydrophilic drug
loaded, via direct subcomponent self-assembly of block copolymer
poly(ethyleneglycol)-block-poly(L-lysine) (PEG-b-PLys), 2-formylbenzeneboronic
acid (2-FPBA) and hydrophilic 1,2-diol-containing drugs (e.g. capecitabine
(CAPE)) under physiological pH 7.4 based on the synergistic formation of an
iminoboronate structure. The PEG-b-PLys/2-FPBA micelles without CAPE are
well-characterized in terms of micellization mechanism, size, morphology, pH-
and GSH-responsiveness. Encapsulation of CAPE by forming PEG-b-PLys/2-FPBA/CAPE
complex micelles via synergistic formation of the iminoboronate structure is
discussed and pH-and GSH-responsive drugrelease studies are carried out. The
complex micelles are stable under physiological neutral conditions but could be
destroyed in response to the stimuli of physiological acidic condition (pH 5.0)
and/or glutathione (GSH) at pH 7.4. pH- and GSH-responsive drug-releases are
successfully achieved. The drug-loaded complex micelles could be endocytosed by
HepG2 cells and efficiently deliver hydrophilic drugs into them. This type of
complex micelles could be used as a promising platform for the delivery of
hydrophilic 1,2-diol-containing drugs.
