of non-stoichiometric IPECs, since charges at sites in the inner parts of the
molecules can be inaccessible to the oppositely charged polyelectrolyte.
Mismatching charge densities leads to a higher degree of swelling of the colloidal
particles. It is proposed that these colloidally stable IPEC particles consist of
a charge-neutralized core, in which 1:1 stoichiometry and high entanglements
prevails, and an outer shell consisting of a few polyelectrolyte layers whose charges
are not completely compensated, giving the complex its net charge, stabilizing
the particles, and preventing them from further aggregation. The number of polymer chains included in a single IPEC particle varies from hundreds of chains in
extremely dilute systems up to several thousands for more concentrated
component solutions [47].
With Steric Stabilization
In the previous situation, the particles were stabilized mainly by the charges in the
outer shell (electrostatic stabilization). Another type of stabilization for colloids is
steric stabilization, which can be introduced in the case of polyplexes by the
presence of a neutral hydrophilic block in the polycation. Micelle-like structures
are thus obtained consisting of a charge-neutralized core, in which 1:1 stoichiometry and high entanglements prevails, and an outer shell consisting of a neutral
hydrophilic block, stabilizing the particles via steric interactions. These IPEC
micelles are also called complex coacervate core micelles (CCCM or C3M)
[52]. This allows, even at charge neutralization and despite possible secondary
aggregation, the colloids to stay in solution stabilized by their polymeric hydrophilic shell. Secondary aggregation occurs when the particles in solution try to
minimize contact with their surroundings (water) at charge neutralization; the
particles will adhere with each other and finally the entire dispersion may coalesce.
Usually, the higher the molecular weight of the polymer and the larger the thickness
of its hydration shell, the more stable are the colloids. In the most efficient cases of
steric stabilization, secondary aggregation can be avoided and single particles are
present in solution, even if neutral. If the stabilization is slightly less efficient, the
aggregates that are nevertheless stable can be redispersed by the addition of more
polycation. The additional polymer is included in the polyplexes leading to a
positive net charge, which introduces repulsion between the particles (Scheme 9).
Poly(ethylene glycol) (PEG) is the polymer that is most used for steric stabilization due to its biocompatibility. It should be noted that random copolymers are
usually not as effective in steric stabilization as block or graft copolymers.
In most of the studies, unfortunately, physico-chemical characterization is not
conducted in enough detail that the size and surface charge of the various species
present in solution are determined; usually, only the properties of the colloidal
suspensions (sum of species) are determined. Indeed, when polycations are added in
high excess to polyplexes after charge neutralization, it seems that in most cases
polycations and neutral polyplexes coexist in solution because the polycations do
not adsorb at the surface of the polyplexes. A way of determining the real size and
surface charge of the polyplexes would be to separate the colloids from the
118
A. Bertin
molecules can be inaccessible to the oppositely charged polyelectrolyte.
Mismatching charge densities leads to a higher degree of swelling of the colloidal
particles. It is proposed that these colloidally stable IPEC particles consist of
a charge-neutralized core, in which 1:1 stoichiometry and high entanglements
prevails, and an outer shell consisting of a few polyelectrolyte layers whose charges
are not completely compensated, giving the complex its net charge, stabilizing
the particles, and preventing them from further aggregation. The number of polymer chains included in a single IPEC particle varies from hundreds of chains in
extremely dilute systems up to several thousands for more concentrated
component solutions [47].
With Steric Stabilization
In the previous situation, the particles were stabilized mainly by the charges in the
outer shell (electrostatic stabilization). Another type of stabilization for colloids is
steric stabilization, which can be introduced in the case of polyplexes by the
presence of a neutral hydrophilic block in the polycation. Micelle-like structures
are thus obtained consisting of a charge-neutralized core, in which 1:1 stoichiometry and high entanglements prevails, and an outer shell consisting of a neutral
hydrophilic block, stabilizing the particles via steric interactions. These IPEC
micelles are also called complex coacervate core micelles (CCCM or C3M)
[52]. This allows, even at charge neutralization and despite possible secondary
aggregation, the colloids to stay in solution stabilized by their polymeric hydrophilic shell. Secondary aggregation occurs when the particles in solution try to
minimize contact with their surroundings (water) at charge neutralization; the
particles will adhere with each other and finally the entire dispersion may coalesce.
Usually, the higher the molecular weight of the polymer and the larger the thickness
of its hydration shell, the more stable are the colloids. In the most efficient cases of
steric stabilization, secondary aggregation can be avoided and single particles are
present in solution, even if neutral. If the stabilization is slightly less efficient, the
aggregates that are nevertheless stable can be redispersed by the addition of more
polycation. The additional polymer is included in the polyplexes leading to a
positive net charge, which introduces repulsion between the particles (Scheme 9).
Poly(ethylene glycol) (PEG) is the polymer that is most used for steric stabilization due to its biocompatibility. It should be noted that random copolymers are
usually not as effective in steric stabilization as block or graft copolymers.
In most of the studies, unfortunately, physico-chemical characterization is not
conducted in enough detail that the size and surface charge of the various species
present in solution are determined; usually, only the properties of the colloidal
suspensions (sum of species) are determined. Indeed, when polycations are added in
high excess to polyplexes after charge neutralization, it seems that in most cases
polycations and neutral polyplexes coexist in solution because the polycations do
not adsorb at the surface of the polyplexes. A way of determining the real size and
surface charge of the polyplexes would be to separate the colloids from the
118
A. Bertin