Biomedical Engineering Reference
In-Depth Information
shell. With an increase in temperature, the PNIPAM collapsed and enclosed
the PCL core, while the PAsp penetrated through the PNIPAM shell, leading
to the formation of negatively charged PAsp channels on the micelle surface.
The release behavior of ionic drugs from the complex micelles was remarkably
different from that of usual core-shell micelles, where diffusion and solubility
of the drugs played a key role. Specifically, it was mainly dependent on the
conformation of the PAsp chains and the electrostatic interaction between the
PAsp and the drugs, which could partially counteract the influence of the pH-
dependent diffusion and solubility of the drugs. As a result, the variation of
drug release rate with pH value was suppressed, which was favorable for
acquiring a relatively steady plasma drug concentration.
d n 4 y 3 n g | 7
9.4 Polyion Complex Micelles for Drug Delivery
Polyion complex (PIC) micelles generally consist of an electrostatically
crosslinked core of two kinds of oppositely charged polyelectrolyte and a
hydrophilic shell of PEG. This kind of complex micelle has an advantage in
delivery of bioactive substances, such as genes, peptides, etc. This section will
cover the recent developments of PIC micelles in drug and gene delivery. The
excellent properties of PIC micelles for in vivo DNA delivery have been
confirmed so far: a diameter around 100 nm with a PEG palisade which
enables complexes to avoid recognition by reticuloendothelial systems,
increased nuclease resistance, increased tolerance under physiological condi-
tions, and excellent gene expression in a serum-containing medium.
PIC micelles were firstly reported by Kataoka et al. 23,24 in the 1990s. The
PIC micelles are formed when a block copolymer with a neutral hydrophilic
block and an ionic block is mixed with counter-charged compounds. The PIC
micelles have a core-shell structure with a core consisting of the polyion
complexes and a shell comprising the neutral block, as indicated in
Figure 9.16. 25 The main driving force for the formation of the PIC micelles
is the electrostatic attraction between the ionic block and the counter-charged
compounds. Various types of biopharmaceuticals, such as plasmid DNA,
oligo-DNA, siRNA, proteins, etc., have been reported as the counter-charged
compounds which can form PIC micelles. 26 The application of PIC micelles in
drug delivery fields is rapidly increasing due to simple and efficient
encapsulation of biopharmaceuticals and outstanding biocompatibility among
various polymer-based drug delivery carriers. The change of ionic strength or
pH-dependent protonation-deprotonation can be useful for the selective
dissociation of PIC micelles. The release of encapsulated biopharmaceuticals
of PIC micelles can be effectively controlled by degradation of the chemical
bonds in the block copolymer responding to the change of pH or reduction
potential.
Kataoka et al. 27 have reported PIC micelles of pDNA with acetal-
poly(ethylene glycol)-block-poly[2-(dimethylamino)ethyl methacrylate] (acetal-
PEG-PAMA) as the gene carrier system. The block copolymer effectively
 
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