shape, and surface chemistries are also expected to influence the drug delivery
performance of PEC nanoparticles, detailed reports on these influencing factors are
rare. More reports are available on drug delivery systems based on other nonnanoparticle PEC systems like hydrogels or layered films (PEM), from which
nanoparticle PEC systems can also be prepared or from which interesting analogies
can be drawn, as in a recent article by Ball and coworkers [117]. Therefore, we
think it useful to review some reports on nanoparticle and non-nanoparticle macroscopic PEC systems (see Sect. 5.2.1) before we discuss drug-loaded PEC particles
(see Sect. 5.2.2).
5.2.1 Drug-Loaded Macroscopic PEC Systems
In the past, concepts have been developed on loading not only of nanoscopic PEC
particles but also of macroscopic PEC systems like microcapsules, hydrogels, or
membranes with drugs aiming at a local or systemic release of the drug in the
human body or in vitro systems. For such purposes, PEC material is prepared from
biorelated PELs like polysaccharides, polypeptides or polynucleotides, for which a
biocompatibility exceeding that of synthetic PEL might be expected. Examples of
reports on the ability of PEC systems to load and release drugs in a retarded manner
are numerous.
Early studies on drug release from non-particular PEC systems have been
reported by Siegel et al. [118]. The model drug caffeine was incorporated and
released from a PEC hydrogel consisting of anionic poly(methylmethacrylate) and
cationic poly(dimethylaminoethylmethacrylate) crosslinked by divinylbenzene.
Caffeine was released at rates varying sharply with pH. At pH ¼ 7.3 no caffeine
was released, whereas at pH ¼ 5 (moderate) and pH ¼ 3 (highest) caffeine was
released with near-zero-order kinetics. Furthermore, the release of caffeine was
found to be associated with water uptake at pH ¼ 3 and pH ¼ 5, and based on this
finding the authors claimed evidence for a moving front mechanism for sorption
and release. Also, Shiraishi et al. [112] reported release of indomethacin from PEC
hydrogel beads consisting of CHT and tripolyphosphate (TPP), focusing on molecular weight effects of CHT in the range of 7,600–83,000 g/mol. The authors found
decreasing release rates with increasing CHT molecular weight in both in vitro and
in vivo systems and found that a medium molecular weight of 25,000 g/mol was
best suited for their application. The authors claimed that decreasing porosity and
increasing tortuosity of the PEC matrix with increasing molecular weight were
crucial molecular properties. They stated that low molecular weight CHT was able
to complex with TPP to form loose and easy hydratable structures, so that hydrophobic indomethacin can be better dissolved. By contrast, PEC of high molecular
weight CHT and TPP had a rather compact structure with smaller porosity and
worse accessibility for water. Further reports on this issue are those of Akbuga
and coworkers [119, 120], who loaded CHT/polyphosphate beads with piroxicam
and calcitonin.
For the description of kinetic drug release data from hydrogel-like materials, the
Ritger–Peppas equation [121] is frequently used according to C DRUG (t) ¼ at
b ,
236
M. M€ uller
performance of PEC nanoparticles, detailed reports on these influencing factors are
rare. More reports are available on drug delivery systems based on other nonnanoparticle PEC systems like hydrogels or layered films (PEM), from which
nanoparticle PEC systems can also be prepared or from which interesting analogies
can be drawn, as in a recent article by Ball and coworkers [117]. Therefore, we
think it useful to review some reports on nanoparticle and non-nanoparticle macroscopic PEC systems (see Sect. 5.2.1) before we discuss drug-loaded PEC particles
(see Sect. 5.2.2).
5.2.1 Drug-Loaded Macroscopic PEC Systems
In the past, concepts have been developed on loading not only of nanoscopic PEC
particles but also of macroscopic PEC systems like microcapsules, hydrogels, or
membranes with drugs aiming at a local or systemic release of the drug in the
human body or in vitro systems. For such purposes, PEC material is prepared from
biorelated PELs like polysaccharides, polypeptides or polynucleotides, for which a
biocompatibility exceeding that of synthetic PEL might be expected. Examples of
reports on the ability of PEC systems to load and release drugs in a retarded manner
are numerous.
Early studies on drug release from non-particular PEC systems have been
reported by Siegel et al. [118]. The model drug caffeine was incorporated and
released from a PEC hydrogel consisting of anionic poly(methylmethacrylate) and
cationic poly(dimethylaminoethylmethacrylate) crosslinked by divinylbenzene.
Caffeine was released at rates varying sharply with pH. At pH ¼ 7.3 no caffeine
was released, whereas at pH ¼ 5 (moderate) and pH ¼ 3 (highest) caffeine was
released with near-zero-order kinetics. Furthermore, the release of caffeine was
found to be associated with water uptake at pH ¼ 3 and pH ¼ 5, and based on this
finding the authors claimed evidence for a moving front mechanism for sorption
and release. Also, Shiraishi et al. [112] reported release of indomethacin from PEC
hydrogel beads consisting of CHT and tripolyphosphate (TPP), focusing on molecular weight effects of CHT in the range of 7,600–83,000 g/mol. The authors found
decreasing release rates with increasing CHT molecular weight in both in vitro and
in vivo systems and found that a medium molecular weight of 25,000 g/mol was
best suited for their application. The authors claimed that decreasing porosity and
increasing tortuosity of the PEC matrix with increasing molecular weight were
crucial molecular properties. They stated that low molecular weight CHT was able
to complex with TPP to form loose and easy hydratable structures, so that hydrophobic indomethacin can be better dissolved. By contrast, PEC of high molecular
weight CHT and TPP had a rather compact structure with smaller porosity and
worse accessibility for water. Further reports on this issue are those of Akbuga
and coworkers [119, 120], who loaded CHT/polyphosphate beads with piroxicam
and calcitonin.
For the description of kinetic drug release data from hydrogel-like materials, the
Ritger–Peppas equation [121] is frequently used according to C DRUG (t) ¼ at
b ,
236
M. M€ uller