Biomedical Engineering Reference
In-Depth Information
A
Self-assembly
Doxorubicin
PEG
45
-PLA
8
-PLP
19
Ketal cross-linker
Endosome
(pH~5.0)
Nucleus
DOX release
(a) 1 min
B
C
(a)
(b)
(c)
(d)
(e)
2.5
2.0
1.5
1.0
δ
(ppm)
(b) 1 h
2.5
2.0
1.5
1.0
(c) 3 h
δ
(ppm)
2.5
2.0
1.5
1.0
δ
(ppm)
Figure 15.4
(A) Illustration of the DOX-loaded nanogels with a pH-labile ketal
crosslinker and intracellular release of DOX triggered by the endosomal pH. (B) Proton
nuclear magnetic resonance
(
1
H NMR) spectra of
K
-nanogel in deuterium oxide at pH
5.0 at various incubation periods and the postulated corresponding structures of ketal
crosslinked shell domains. Arrows indicate the gradual disappearance of ketal peaks.
(C) Confocal laser scanning microscopy (CLSM) microimages of MCF-7 cells incubated
with (a) free DOX for 1 h, (b) DOX-
K
-nanogel for 1 h, (c) DOX-
K
-nanogel for 5 h, (d)
DOX-nanogel for 1 h and (e) DOX-nanogel for 5 h (equivalent 5 μg mL
-1
DOX; green
l uorescence is associated with LysoTracker and the red l uorescence is expressed by free
DOX and released DOX). Scale bar = 20 μm. Reproduced with permission from [69].
(P(LGA-
co
-CLG)) block copolymers were prepared by the initiator-free
photocrosslinking [64]. As pH increased from 4.0 to 7.4, there was a sig-
nii cant increase in the hydrodynamic radii (
R
h
s) of nanogels attributed
to the swelling of polypeptide cores induced by the gradual ionizations
of LGA residues. Drug-loaded nanogels were prepared through the mix-
ture of PEG-P(LGA-
co
-CLG) copolymers with a model drug, rifampin,
and subsequent
in situ
photocrosslinking. h e rifampin-loaded nanogels
exhibited a faster drug release at pH 7.4 compared to that at pH 4.0 due to
the swelling of the nanogels at neutral or alkaline condition.
