Biomedical Engineering Reference
In-Depth Information
In addition to disulfide linkages, the hydrolysis capability of ester (including
acid-labile ester) or amide bonds also has been widely used to create
biodegradable PEI-based gene vectors. These vectors can be degraded into
nontoxic LMW PEIs without inducing toxicity or immune response. However,
common hydrolysis degradation is unspecific and hard to control, while
acidic hydrolysis would damage the nucleic acids due to the low pH of
late endosomes (or lysosomes). Endres et al. synthesized amphiphilic PEG-
PCL-PEI triblock copolymers as self-assemble multifunctional carriers
(Scheme 4.4A).
26
The synthesis was in three steps: (1) PEG-PCL was produced
by ring-opening polymerization initiated by the PEG hydroxyl endgroup,
using Sn(Oct)
2
as a catalyst; (2) a double bond was attached onto the PEG-
PCL chain-end by esterification of the PEG-PCL hydroxyl group with acryloyl
chloride; (3) 2,500 kDa PEI was coupled onto the PEG-PCL-linker copolymer
by Michael addition. The authors found that increasing the hydrophilicity
resulted in a stability increase, combined with a decrease in cytotoxicity due to
effective PEG charge shielding.
d
n
4
y
3
n
g
|
3
Scheme 4.4
Synthesis of biodegradable PEI derivatives.
