Biomedical Engineering Reference
In-Depth Information
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Figure 7.7
(A) Effect of pH on the scattering intensity (N) and zeta-potential (m)of
PEG
115
-b-(PrMA
28
-co-MAA
53
)/AON/G5 PAMAM-based PICMs. (B)
Proposed mechanism of shell dissociation. (C) Bcl-2 gene silencing in PC-
3 cells transfected for 5 h with AON (400 nM) or siRNA (25 nM)
complexed to G5 PAMAM or entrapped in plain or Fab9-PEG
115
-b-
P(PrMA
28
-co-MAA
53
)/G5 or G3 PAMAM PICMs at an N/(P+COO
-
)
ratio of 1.5 (AON: antisense oligonucleotides). (Adapted from Elsabahy
et al.
96
with permission from Wiley.)
procedure (disulfide linkage) employed to attach the targeting ligand to PEG-b-
P(PrMA-co-MAA) was relatively inefficient and potentially subject to cleavage
in the blood, then anti-CD71 Fab9 was conjugated to a modified amino-PEG-b-
P(PrMA-co-MAA) via a maleimide/activated ester bifunctional linker with a
more stable sulfide bond.
97
7.3.2.2 Redox-Responsive Polymeric Micelles
Chemical reactions involving the reductive degradation of disulfide bonds of
polymers by intracellular glutathione (GSH) have been widely investigated for
responsive drug and gene delivery.
98-100
GSH is a thiol-containing tripeptide
and reduces disulfide bonds in the cytoplasm. It has been demonstrated that
the intracellular concentration of GSH (ca. 10 mM) is significantly higher than
