Biomedical Engineering Reference
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a
b
+
Self-assembly
PEO-
b
-polycationimer
Positively charged
DNA
Negatively charged
Polyion micelles formed by
electrostatic attaction
Fig. 15
(a
) Schematic of the proton-sponge mechanism. Protonation of the proton-sponge polymer
(
green
) causes increased influx of protons (and counter-ions) into endocytic vesicles. Increasing
osmotic pressure causes the vesicle to swell and rupture (Reproduced from Pack et al.
2005
with
permission). (
b
) Schematic illustration of formation of polyion complex (PIC) micelles from
amphiphilic copolymer and DNA
their easy synthesis and flexible chemistry in their structures. For example, PEO-
poly(L-lysine) (PEO-PLL) micelles have been extensively used for application in
gene delivery because the amine-contained core-forming block can form a stable
polyion complex with DNA through an electrostatic interaction (Ward et al.
2002
;
Lee et al.
2005b
; Katayose and Kataoka
1997, 1998
; Kakizawa et al.
1999, 2001
;
Harada et al.
2001
; Miyata et al.
2004
; Meister and Anderson
1983
; Behr
1997
;
Boussif et al.
1995
). PEO
—
PLL micelles were injected via superior mesenteric
vein and showed sustained gene expression in the liver for 3 days. However,
PEO
—
PLL has high CMC and may dissociate upon dilution.
To increase the stability of PEO-PLL micelles against dissociation, PEO-PLL
micelles with crosslinked core were prepared by substituting certain fractions of the
lysine residues in the PLL core with thiol groups which can readily form disulfide
cross-links with other sulfide substituted PEO-PLL polymers and develop a net-
work structure in the micelle core after DNA complexation (Kakizawa et al.
1999,
2001
; Harada et al.
2001
). The cross-linked core of the micelles can be cleaved
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