Biomedical Engineering Reference
In-Depth Information
capsules was observed compared with dextran/CH-paired polyelectrolytes [108]. Gelatin is a weakly
charged polyelectrolyte with low-charge density. This may result in formation of a loopy conforma-
tion at coating conditions and lead to adsorption of several monomolecular protein layers [153].
The suggestion was verifi ed during QCM study of gelatin/PSS assembly, because the averaged fre-
quency shift was 483 Hz for each gelatin layer, which corresponds to a thickness of 8 nm. Obviously,
a single gelatin layer is much thinner than this.
Most polyelectrolyte shells are composed of one weak base and one strong acid (e.g., PAH/PSS,
CH/dextran sulfate). It should be observed that permeability of shells built on these paired poly-
electrolytes would not change much upon pH variations. For example, PAH/PSS multilayers have
slightly higher (1.5 times) permeability at pH 1.4 than that at pH 7.4 [154]. The possible reason is
that the charge of weak base PAH is relatively stable at different pH values, and interactions with
PSS are not signifi cantly affected. Similarly, CH/dextran sulfate is weak base-strong acid combi-
nation and obvious pH effects were not observed. When strong acid was replaced by weak acids
such as carboxymethyl cellulose sodium salt or alginate, similar release profi les were noticed at
pH 7.4. This indicates that the strength of the ionic groups on the polymer chains may not signifi -
cantly infl uence the permeability of the polysaccharide multilayers [154]. The pH stability of above
formulations may be advantageous in oral administration because of insensitivity to GI tract's pH
variation.
10.3.6 C ARRIER S URFACE F UNCTIONALIZATION
10.3.6.1
PEGylation of Polyelectrolyte Shells
Poly(ethylene glycol) (PEG), a noncharged hydrophilic polymer, is well-accepted in pharmaceutical
industry for drug formulation. When incorporated onto liposomes, it has shown the effects to prolong
blood circulation time and improve drug pharmacokinetics [163]. Polyelectrolyte shells represent
certain charges on their surfaces that may not be ideal for intravenous injection because of hemo-
compatibility concerns and sequestration by the mononuclear phagocytic system (MPS) in liver
and spleen. PEGylation on shell surface provides a reasonable solution. It has been demonstrated
that PEG can be linked to polycation PAH outermost layer as a last step during drug crystal coat-
ing process [155]. This modifi cation was accomplished by the covalent attachment of mPEG-SPA
to a PAH layer of the encapsulated drug particles via the reaction between the hydroxysuccinimi-
dyl (NHS) moiety of mPEG-SPA with an amine on PAH. The requirement for this reaction to
take place is keeping the pH of the buffered solution between 8.2 and 8.5. At this basic pH, the
protonated amine of the PAH layer becomes deprotonated and PEG can be covalently attached to
this secondary amine. Consequently, incorporation of PEG to the nanoshell of the encapsulated
drug particle created neutralization in charge of the nanoparticle. Successful PEG conjugation was
verifi ed as the particle surface zeta-potential dropped from positive 25 mV to near zero. XPS study
further demonstrated the conjugation of PEG to PAH as apparent increase in C
-
(O,N) (286.34 eV)
peak area and decrease in C
=
O, C
-
F (287.64 eV) peak area compared with PAH-coated drug
crystals.
In a study of cell interactions with LbL capsules, PEGylation reduced nonspecifi c protein
adsorption onto polyelectrolyte capsule surface [51]. PEI-PEG copolymers with PEI/PEG graft
ratios (1, 5, and 10) were synthesized and used as the outermost layers for shell assembly. Compared
with PEI outermost layer covered capsules, all PEI-PEG covered ones had much less changes in
surface zeta-potential after serum contact. It indicated that the shielding property of PEG could
effectively deter protein adsorption [164].
10.3.6.2
Active Targeting of Capsules
Effective delivery of therapeutic agents to the diseased site requires that the carriers have targeting
moieties, which recognize highly expressed antigens or receptors on cell surface. One strategy to
 
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