PEC/Polynucleotide Carriers
In the early work of Kabanov et al., PEC particles of DNA and poly(N-ethyl-4vinylpyridinium) were shown to effectively transfect mammalian cells, especially
when administered with poly(ethylene oxide)-block-poly(propylene oxide)-blockpoly(ethylene oxide) copolymer (Pluronic P85) [127]. Later nanoparticular systems
of crosslinked nanogels of PEI and poly(ethylene oxide) (PEO) were developed for
the delivery of oligonucleotides by these authors [128]. Also, Kataoka et al.
contributed to PEC-mediated delivery of antisense oligonucleotides complexed
with a copolymer of ethylene glycol and lysine (PEG-co-Lys) under physiological
conditions [129]. Note that in these systems the drug (oligo/polynucleotide) is also
one of the complexing components. The triggerable release of nucleic acids was
recently reviewed by Soliman et al. [130], who discussed temperature, redox
potential, and light triggers in PEC systems.
Small Drug-Loaded PEC Particles
Numerous reports are available on binary drug/PEL complex (nano)particles,
where a charged drug is complexed by an oppositely charged PEL. For
example, Kim and Nujoma complexed cationic oxprenolol with a copolymer of
methylmethacrylate and sodium methacrylate (PMMA/MANa), forming gel beads
from which the drug was released in a retarded manner in dependence of pH by a
combined swelling/erosion mechanism [131]. More recently, Jimenez-Kairuz et al.
[132] reported high loading of swellable complexes of model drugs (atenolol,
lidocain hydrochloride) and anionic carbomers and their release. Very recently,
Cheow and Hadinoto [133] reported nanoparticular ciprofloxacin/DS complexes
(200–400 nm, 80% drug loading), which showed a dissolution rate twice that of the
poorly soluble free drug crystals.
However, exclusively ternary PEC nanoparticles consisting of complexed
polycation and polyanion and loaded by low molecular weight organic drug
compounds (PC/PA/drug) with a size range of 10–500 nm shall be reviewed herein.
One of the first reports on the usage of ternary drug/PEC nanoparticles for small
pharmaceutical drug delivery applications was from Tiyaboonchai et al. [134]. The
authors described how the fungicide drug amphotericin B (AMB) can be uploaded
and released from PEC coacervate particles consisting of PEI and DS in the
presence of zinc sulfate as ionic crosslinker and manitol as redispersing agent. As
colloid parameters, PEI/DS particles featured a zeta potential of around 30 mV,
spherical particle shape with diameters in the range 100–600 nm (PDI ¼ 0.2),
which could be controlled by pH, mixing ratio, and concentration. A fast release
of AMB was found, which could be modulated by pH and the presence of surfactant
in the release medium (HEPES) (Fig. 29). AMB/PEC particles showed no toxicity
against HeLa cells and were able to kill Candida albicans (human fungal test
strain).
At the same time, Alonso and coworkers [135] reported doxorubicin (DOX)loaded PEC particles of CHT and DS. DOX loadings of up to 4% could be achieved
238
M. M€ uller
In the early work of Kabanov et al., PEC particles of DNA and poly(N-ethyl-4vinylpyridinium) were shown to effectively transfect mammalian cells, especially
when administered with poly(ethylene oxide)-block-poly(propylene oxide)-blockpoly(ethylene oxide) copolymer (Pluronic P85) [127]. Later nanoparticular systems
of crosslinked nanogels of PEI and poly(ethylene oxide) (PEO) were developed for
the delivery of oligonucleotides by these authors [128]. Also, Kataoka et al.
contributed to PEC-mediated delivery of antisense oligonucleotides complexed
with a copolymer of ethylene glycol and lysine (PEG-co-Lys) under physiological
conditions [129]. Note that in these systems the drug (oligo/polynucleotide) is also
one of the complexing components. The triggerable release of nucleic acids was
recently reviewed by Soliman et al. [130], who discussed temperature, redox
potential, and light triggers in PEC systems.
Small Drug-Loaded PEC Particles
Numerous reports are available on binary drug/PEL complex (nano)particles,
where a charged drug is complexed by an oppositely charged PEL. For
example, Kim and Nujoma complexed cationic oxprenolol with a copolymer of
methylmethacrylate and sodium methacrylate (PMMA/MANa), forming gel beads
from which the drug was released in a retarded manner in dependence of pH by a
combined swelling/erosion mechanism [131]. More recently, Jimenez-Kairuz et al.
[132] reported high loading of swellable complexes of model drugs (atenolol,
lidocain hydrochloride) and anionic carbomers and their release. Very recently,
Cheow and Hadinoto [133] reported nanoparticular ciprofloxacin/DS complexes
(200–400 nm, 80% drug loading), which showed a dissolution rate twice that of the
poorly soluble free drug crystals.
However, exclusively ternary PEC nanoparticles consisting of complexed
polycation and polyanion and loaded by low molecular weight organic drug
compounds (PC/PA/drug) with a size range of 10–500 nm shall be reviewed herein.
One of the first reports on the usage of ternary drug/PEC nanoparticles for small
pharmaceutical drug delivery applications was from Tiyaboonchai et al. [134]. The
authors described how the fungicide drug amphotericin B (AMB) can be uploaded
and released from PEC coacervate particles consisting of PEI and DS in the
presence of zinc sulfate as ionic crosslinker and manitol as redispersing agent. As
colloid parameters, PEI/DS particles featured a zeta potential of around 30 mV,
spherical particle shape with diameters in the range 100–600 nm (PDI ¼ 0.2),
which could be controlled by pH, mixing ratio, and concentration. A fast release
of AMB was found, which could be modulated by pH and the presence of surfactant
in the release medium (HEPES) (Fig. 29). AMB/PEC particles showed no toxicity
against HeLa cells and were able to kill Candida albicans (human fungal test
strain).
At the same time, Alonso and coworkers [135] reported doxorubicin (DOX)loaded PEC particles of CHT and DS. DOX loadings of up to 4% could be achieved
238
M. M€ uller