particles >300 nm or by keeping at least one dimension of the particle on a
length scale of >100 nm to prevent accumulation in the liver and maintaining at
least two dimensions at <200 nm to allow the particles to navigate the sinusoids
of the spleen. Also, a low polydispersity index has been discussed as a requirement for cellular uptake [110, 111].
2. Nanoparticle geometry (shape) plays a key role in particle internalization, but
optimum parameters for engineered nanoparticles have yet to be determined
[112]. Spherical morphology and a low polydispersity index are generally
claimed to be advantageous for cellular uptake. To name only one example,
spherical and nonspherical polystyrene microparticles were incubated with
macrophages (phagocytosis) by Champion and Mitragotri [113]. These authors
demonstrated that spherical particles were readily internalized due to their
symmetry, whereas elliptical disk-shaped particles were only internalized
when their first contact was along the major and not the minor axis.
3. Surface chemistry has three vital roles in the function of engineered
nanoparticles, i.e., control of opsonization, which ultimately dictates the
reticulo-endothelial-system (RES) response; cellular targeting; and organellae
targeting via ligands known to bind cell or organellae surface receptors [112].
Favorable in that respect are nanoparticles bearing a surface charge magnitude
larger than 30 mV (+/À) [114, 115]. Furthermore, Harada and Kataoka point out
that particles bearing a hydrophilic corona are advantageous for prolonged
circulation time, low uptake by RES, low nonspecific protein adsorption, and
solubilization of hydrophobic drugs in the micellar core [116].
4. In the line of Petros and DeSimone [107], it has to be emphasized that the
“tailored release of therapeutics still represents a key barrier in the field of
engineered nanoparticles,” which in our understanding of DDS is a very important remark. We see (without criticism) a certain preference in the nanomedicine
and drug/nanoparticle literature for phenomena like tailored drug uptake, toxicology, and cell interaction, whereas tailored drug release related to molecular
understanding of pharmacodynamics is of minor interest (“drug release will take
place anyway”). In that framework, predominant strategies so far incorporate
materials that are enzymatically degradable, pH-sensitive or reductively labile,
which facilitate breaking or destabilizing bonds between drug and carrier on
reaching the intended site of action. Further efforts should be directed to
molecular structures and mechanisms allowing tailored release (not only uptake)
kinetics of one or multiple drugs according to the specific requirements of
clinicians.
5.2 Drug Delivery from PEC Systems
Interestingly, PEC nanoparticles do not fall directly into one of the nanomedicine
classes denoted or defined in classical review papers like that of Duncan and Gaspar
[105], although their controllable sizes (20–500 nm), shapes (spheres, rods), and
surface chemistries match well those of nanomedicine. However, although size,
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
235
length scale of >100 nm to prevent accumulation in the liver and maintaining at
least two dimensions at <200 nm to allow the particles to navigate the sinusoids
of the spleen. Also, a low polydispersity index has been discussed as a requirement for cellular uptake [110, 111].
2. Nanoparticle geometry (shape) plays a key role in particle internalization, but
optimum parameters for engineered nanoparticles have yet to be determined
[112]. Spherical morphology and a low polydispersity index are generally
claimed to be advantageous for cellular uptake. To name only one example,
spherical and nonspherical polystyrene microparticles were incubated with
macrophages (phagocytosis) by Champion and Mitragotri [113]. These authors
demonstrated that spherical particles were readily internalized due to their
symmetry, whereas elliptical disk-shaped particles were only internalized
when their first contact was along the major and not the minor axis.
3. Surface chemistry has three vital roles in the function of engineered
nanoparticles, i.e., control of opsonization, which ultimately dictates the
reticulo-endothelial-system (RES) response; cellular targeting; and organellae
targeting via ligands known to bind cell or organellae surface receptors [112].
Favorable in that respect are nanoparticles bearing a surface charge magnitude
larger than 30 mV (+/À) [114, 115]. Furthermore, Harada and Kataoka point out
that particles bearing a hydrophilic corona are advantageous for prolonged
circulation time, low uptake by RES, low nonspecific protein adsorption, and
solubilization of hydrophobic drugs in the micellar core [116].
4. In the line of Petros and DeSimone [107], it has to be emphasized that the
“tailored release of therapeutics still represents a key barrier in the field of
engineered nanoparticles,” which in our understanding of DDS is a very important remark. We see (without criticism) a certain preference in the nanomedicine
and drug/nanoparticle literature for phenomena like tailored drug uptake, toxicology, and cell interaction, whereas tailored drug release related to molecular
understanding of pharmacodynamics is of minor interest (“drug release will take
place anyway”). In that framework, predominant strategies so far incorporate
materials that are enzymatically degradable, pH-sensitive or reductively labile,
which facilitate breaking or destabilizing bonds between drug and carrier on
reaching the intended site of action. Further efforts should be directed to
molecular structures and mechanisms allowing tailored release (not only uptake)
kinetics of one or multiple drugs according to the specific requirements of
clinicians.
5.2 Drug Delivery from PEC Systems
Interestingly, PEC nanoparticles do not fall directly into one of the nanomedicine
classes denoted or defined in classical review papers like that of Duncan and Gaspar
[105], although their controllable sizes (20–500 nm), shapes (spheres, rods), and
surface chemistries match well those of nanomedicine. However, although size,
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
235