Biomedical Engineering Reference
In-Depth Information
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Figure 4.4
Schematic illustration of decorating strategies to obtain low-toxicity PEI-
based vectors: (A) biocompatible PEI derivatives; (B) biodegradable
crosslinked PEIs.
20 kDa) onto branched PEI (25 kDa); the results have shown favorable
transfection efficiency and reduced cytotoxicity in small interfering RNA
(siRNA), plasmid DNA (pDNA), and messenger RNA (mRNA) delivery
(Scheme 4.1A).
5,6
Merkel et al. reported that in vitro complement activation
was prominently caused by PEI 25 kDa, whereas the PEGylated versions of
PEI 25 kDa showed no significant activity.
7
It was shown that PEGylation of
polycations with 20 kDa PEG or higher molecular weight may be favorable.
Chen et al. synthesized a PEG-g-PEI copolymer by grafting 8 kDa PEG
onto 25 kDa PEI.
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The PEG-g-PEI/pEGFP-C1 nanoparticles displayed low
cytotoxicity, good solubility, and compatibility with serum. They found that
biocompatibility was guaranteed by dense PEG shells, which endowed the
nanoparticles with water solubility and prevented their interaction with serum
protein in the culture medium. Beyerle et al. investigated the side effects of
PEG-g-PEI/siGFP polyplexes in mice lungs.
9
The results showed that
hydrophilic modifications, with high PEG-grafting degrees, induced less
proinflammatory effects without depleting macrophages and disrupting the
epithelial/endothelial
barrier
in
the
lungs,
while
showing
only
a
minor
oxidative stress response.
The length and density of PEG chains conjugated to PEI also have an effect
on transfection efficiency. Weber and co-workers grafted 25 kDa PEI with
20 kDa or 2 kDa PEG to form biocompatible PEI-g-PEG gene vectors. Then
