Biomedical Engineering Reference
In-Depth Information
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Figure 7.2
The formation procedure of polymeric micelles with increased concentra-
tions of block copolymers.
the accommodation of cargo molecules.
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Furthermore, various ligands have
been attached to the hydrophilic shell for active targeting, including different
sugars or peptides, transferrin, and folate. Polymeric micelles can also be
engineered by means of the addition of pH- or redox-sensitive moieties
according to the biological characteristics of the tumor environment.
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In recent years, significant progress has been made in the design of
polymeric siRNA carriers. Polymeric micelles of siRNA can be classified as
following: (a) polymeric micelles formed by the complexation of synthetic
amphiphilic polymers containing polycation segments with siRNA, followed
by micellization of polymer/siRNA complexes; (b) smart polymeric micelles
having pH-responsive capacity or degradable linkages to facilitate siRNA
release intracellularly. Incorporation of targeting ligands on the surface of
carriers under each category has also been tried.
7.3.1 Polymeric Micelles Based on Amphiphilic Polymers for
siRNA Delivery
Kakizawa et al. first developed engineered block copolymers to construct
polyplex micelles useful for siRNA delivery. The micellization behavior of
block copolymers was utilized to prepare organic-inorganic hybrid nanopar-
ticles with a core-shell structure based on the self-assembly of poly(ethylene
glycol)-block-poly(aspartic acid) block copolymers [PEG-P(Asp)] with calcium
phosphate. The nanoparticles had diameters in the range of several hundreds
of nanometers, depending on the PEG-PAA concentration, and revealed
excellent colloidal stability due to the steric repulsion effect of the PEG layer
surrounding the calcium phosphate core. The loading capacities for siRNA
