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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