lowest initial burst behavior and slowest release kinetics were obtained for the
highest PEC concentration (0.01 M) and lowest PAM/PEC ratio (1:20). SFM
images of PAM-loaded (left) and PAM-depleted (right) PEI/CS-0.9 particles are
shown in Fig. 32b (unpublished data). From DLS we obtained hydrodynamic radii
of around 60–90 nm for PAM-loaded PEC nanoparticles and the bare unloaded
PEC particles showed smaller radii.
Furthermore, kinetic analysis based on the Ritger–Peppas model revealed values
of b ( 0.5 (see Sect. 5.2.1) for PAM/PEC samples cast from 0.002 M dispersions,
suggesting dissolution of dried PAM in the PEC matrix. However, PAM/PEC
samples cast from 0.01 M dispersions revealed values of b close to 0.5, suggesting
hindered dissolution or diffusion due to a more dense PEC matrix and lower drug/
surface area ratio. A model describing three levels of retention of PAM in PEC
particle films is suggested and shown in Fig. 32c. On the molecular level, the
negatively charged PAM is bound or condensed at free uncomplexed cationic PEI
sites within small primary PEC particles. On an intraparticular nanoscopic level,
PAM is physically entrapped within single secondary PEC particles of aggregated
primary PEC particles. On an interparticular mesoscopic level, PAM is entrapped
within the zone formed by the surface-aggregated secondary PEC particles upon
solution casting.
5.3 Interaction of PEC Particles with Cells and Biofluids
PEC particles designed for use in the human body must be critically studied for their
cell toxicity, immunoresponse, and cellular interactive properties. Thereby, the
related requirements of PEC particles in systemic pharmaceutical applications are
expected to be even more strict compared to the locally confined particles
introduced in Sect. 5.2.3, since the exposed surface areas recognized by in vitro
or in vivo systems are different. While cast PEC particles films offer less surface
area to cells cultured on top, dispersed PEC particles expose more surface area to
cells in the volume phase. Many reports can be obtained in the open literature on the
toxicology and biocompatibility of DNA/polycation complexes [128, 161], but only
a few are available on other biorelated PEL systems. The development and potential
applications of nontoxic multifunctional PEC particles with respect to targeted
tissue delivery, organelle trafficking, and imaging was reviewed comprehensively
by Hartig et al. [162]. Colloidal stability, hydrodynamic diameter of less than
200 nm, spherical morphology, low polydispersity, and surface charge magnitude
> 30 mV are outlined as key physicochemical parameters for a successful delivery
vehicle or for imaging purposes in the human body. Furthermore, Delair has
reviewed PEC particles of CHT and DS [163] useful in nanomedicine. Some
application examples are small drug delivery [135], growth factor delivery [126,
164], and magnetic resonance imaging using gadolinium-loaded CHT/DS PEC
particles [165]. In the following sections we give examples, modalities, and requirements of PEC nanoparticle systems related to toxicity, immuneresponse, and cell
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
245
highest PEC concentration (0.01 M) and lowest PAM/PEC ratio (1:20). SFM
images of PAM-loaded (left) and PAM-depleted (right) PEI/CS-0.9 particles are
shown in Fig. 32b (unpublished data). From DLS we obtained hydrodynamic radii
of around 60–90 nm for PAM-loaded PEC nanoparticles and the bare unloaded
PEC particles showed smaller radii.
Furthermore, kinetic analysis based on the Ritger–Peppas model revealed values
of b ( 0.5 (see Sect. 5.2.1) for PAM/PEC samples cast from 0.002 M dispersions,
suggesting dissolution of dried PAM in the PEC matrix. However, PAM/PEC
samples cast from 0.01 M dispersions revealed values of b close to 0.5, suggesting
hindered dissolution or diffusion due to a more dense PEC matrix and lower drug/
surface area ratio. A model describing three levels of retention of PAM in PEC
particle films is suggested and shown in Fig. 32c. On the molecular level, the
negatively charged PAM is bound or condensed at free uncomplexed cationic PEI
sites within small primary PEC particles. On an intraparticular nanoscopic level,
PAM is physically entrapped within single secondary PEC particles of aggregated
primary PEC particles. On an interparticular mesoscopic level, PAM is entrapped
within the zone formed by the surface-aggregated secondary PEC particles upon
solution casting.
5.3 Interaction of PEC Particles with Cells and Biofluids
PEC particles designed for use in the human body must be critically studied for their
cell toxicity, immunoresponse, and cellular interactive properties. Thereby, the
related requirements of PEC particles in systemic pharmaceutical applications are
expected to be even more strict compared to the locally confined particles
introduced in Sect. 5.2.3, since the exposed surface areas recognized by in vitro
or in vivo systems are different. While cast PEC particles films offer less surface
area to cells cultured on top, dispersed PEC particles expose more surface area to
cells in the volume phase. Many reports can be obtained in the open literature on the
toxicology and biocompatibility of DNA/polycation complexes [128, 161], but only
a few are available on other biorelated PEL systems. The development and potential
applications of nontoxic multifunctional PEC particles with respect to targeted
tissue delivery, organelle trafficking, and imaging was reviewed comprehensively
by Hartig et al. [162]. Colloidal stability, hydrodynamic diameter of less than
200 nm, spherical morphology, low polydispersity, and surface charge magnitude
> 30 mV are outlined as key physicochemical parameters for a successful delivery
vehicle or for imaging purposes in the human body. Furthermore, Delair has
reviewed PEC particles of CHT and DS [163] useful in nanomedicine. Some
application examples are small drug delivery [135], growth factor delivery [126,
164], and magnetic resonance imaging using gadolinium-loaded CHT/DS PEC
particles [165]. In the following sections we give examples, modalities, and requirements of PEC nanoparticle systems related to toxicity, immuneresponse, and cell
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
245