Premature removal from the circulating blood must be avoided before the target is
reached
Active ingredients must not be leached out
The particles must be taken up in the organ to be treated
The particle itself must be degraded afterwards so that the polymer does not remain
in the body to exert unwanted long term effects.
Here, hydrophilic micro- and nanogels can provide certain advantages. Protein
adsorption or opsonization makes nanoparticles recognizable for phagocytic cells,
but is strongly reduced for hydrogels due to their hydrophilic nature and high water
content [1, 5]. Active ingredients may be linked covalently or entrapped in the
network and released by degradation. Targeting is promoted by the high mobility of
the soft gel particles in the smallest capillaries. As for other nanoparticles, targeting
can be effected by the EPR effect (enhanced permeability and retention) observed
for tumor tissue [6] and by decoration with specific ligands, (e.g., peptides and
glucosides). In contrast to solid nanoparticles, hydrophilic nanogels can be
designed to respond to changes in temperature and pH by a change in the degree
of swelling. Furthermore and due to their open structure, degradability can be
designed to be triggered rather specifically and instantaneously by changes in the
environment. The latter may be achieved by biohybrid nanogels or nanoconetworks, where the biological constituent ensures a specific responsiveness
and degradability. Beyond the scope of this work, modern tools to design biopolymers open further perspectives to introduce specific and predictable bioactive
functions, such as the ability to present receptor-binding ligands, cell-triggered
proteolytic degradation, and natural remodeling.
Here we report on the synthesis and properties of micro-conetworks from
solubilized elastin derivatives using poly(ethylenglycol) (PEG) prepolymers or
bis(sulfosuccinimidyl)suberate (BS3) as crosslinker for the elastin. We demonstrate that such micro-conetworks can be prepared in an easy procedure from
soluble elastin peptides obtained by partial hydrolysis of native elastin. Because
of the biodegradability of the elastin peptide, such hydrogels are fully biodegradable. The molecular weight of the remaining PEG chains is chosen sufficiently low
so that these can be removed from the body via the renal system. In addition to the
biocompatibility and biodegradability, the elastin component provides thermal and
pH-dependent transformation at 35.5 or 37
C and pH 5–7, depending on the
crosslinker used, from a swollen hydrogel to a globular state. Potentially, the
responsiveness of the elastin component to pH and temperature can be exploited
to trigger endosomal uptake in cells and release of drugs bound to the network.
Based on these findings, it appeared attractive to us to prepare hydrophilic microconetworks of soluble elastin, as prepared by standard methods [7]. We expected
that such hydrogel colloids can be prepared even from solubilized elastin samples
that undergo coacervation like the well-defined elastin-like peptides (ELPs)
[8–11], and that such particles can serve as a carrier for drugs where loading and
release as well as internalization by cells can be affected by the volume change
phase transition.
Stimuli-Sensitive Microgels from Native Elastin: An Easy Approach for a Drug. . .
417
reached
Active ingredients must not be leached out
The particles must be taken up in the organ to be treated
The particle itself must be degraded afterwards so that the polymer does not remain
in the body to exert unwanted long term effects.
Here, hydrophilic micro- and nanogels can provide certain advantages. Protein
adsorption or opsonization makes nanoparticles recognizable for phagocytic cells,
but is strongly reduced for hydrogels due to their hydrophilic nature and high water
content [1, 5]. Active ingredients may be linked covalently or entrapped in the
network and released by degradation. Targeting is promoted by the high mobility of
the soft gel particles in the smallest capillaries. As for other nanoparticles, targeting
can be effected by the EPR effect (enhanced permeability and retention) observed
for tumor tissue [6] and by decoration with specific ligands, (e.g., peptides and
glucosides). In contrast to solid nanoparticles, hydrophilic nanogels can be
designed to respond to changes in temperature and pH by a change in the degree
of swelling. Furthermore and due to their open structure, degradability can be
designed to be triggered rather specifically and instantaneously by changes in the
environment. The latter may be achieved by biohybrid nanogels or nanoconetworks, where the biological constituent ensures a specific responsiveness
and degradability. Beyond the scope of this work, modern tools to design biopolymers open further perspectives to introduce specific and predictable bioactive
functions, such as the ability to present receptor-binding ligands, cell-triggered
proteolytic degradation, and natural remodeling.
Here we report on the synthesis and properties of micro-conetworks from
solubilized elastin derivatives using poly(ethylenglycol) (PEG) prepolymers or
bis(sulfosuccinimidyl)suberate (BS3) as crosslinker for the elastin. We demonstrate that such micro-conetworks can be prepared in an easy procedure from
soluble elastin peptides obtained by partial hydrolysis of native elastin. Because
of the biodegradability of the elastin peptide, such hydrogels are fully biodegradable. The molecular weight of the remaining PEG chains is chosen sufficiently low
so that these can be removed from the body via the renal system. In addition to the
biocompatibility and biodegradability, the elastin component provides thermal and
pH-dependent transformation at 35.5 or 37
C and pH 5–7, depending on the
crosslinker used, from a swollen hydrogel to a globular state. Potentially, the
responsiveness of the elastin component to pH and temperature can be exploited
to trigger endosomal uptake in cells and release of drugs bound to the network.
Based on these findings, it appeared attractive to us to prepare hydrophilic microconetworks of soluble elastin, as prepared by standard methods [7]. We expected
that such hydrogel colloids can be prepared even from solubilized elastin samples
that undergo coacervation like the well-defined elastin-like peptides (ELPs)
[8–11], and that such particles can serve as a carrier for drugs where loading and
release as well as internalization by cells can be affected by the volume change
phase transition.
Stimuli-Sensitive Microgels from Native Elastin: An Easy Approach for a Drug. . .
417