44 research outputs found
Modulation of functional pendant chains within poly(ethylene glycol) hydrogels for refined control of protein release
Hydrogels are highly attractive delivery vehicles for therapeutic proteins. Their innate biocompatibility, hydrophilicity and aqueous permeability allow stable encapsulation and release of proteins. The release rates also can be controlled simply by altering the crosslinking density of the polymeric network. However, the crosslinking density also influences the mechanical properties of hydrogels, generally opposite to the permeability. In addition, the release of larger proteins may be hindered below critically diminished porosity determined by the crosslinking density. Herein, the physical properties of the hydrogels are tuned by presenting functional pendant chains, independent of crosslinking density. Heterobifunctional poly(ethylene glycol) monomethacrylate (PEGMA) with various end functional groups is synthesized and copolymerized with PEG dimethacrylate (PEGDA) to engineer PEG hydrogels with pendant PEG chains. The pendant chains of the PEG hydrogels consisting of sulfonate, trimethylammonium chloride, and phenyl groups are utilized to provide negative charge, positive charge and hydrophobicity, respectively, to the hydrogels. The release rates of proteins with different isoelectric points are controlled in a wide range by the type and the density of functional pendant chains via electrostatic and hydrophobic interactions
The significance of peroxisomes in secondary metabolite biosynthesis in filamentous fungi
Peroxisomes are ubiquitous organelles characterized by a protein-rich matrix surrounded by a single membrane. In filamentous fungi, peroxisomes are crucial for the primary metabolism of several unusual carbon sources used for growth (e.g. fatty acids), but increasing evidence is presented that emphasize the crucial role of these organelles in the formation of a variety of secondary metabolites. In filamentous fungi, peroxisomes also play a role in development and differentiation whereas specialized peroxisomes, the Woronin bodies, play a structural role in plugging septal pores. The biogenesis of peroxisomes in filamentous fungi involves the function of conserved PEX genes, as well as genes that are unique for these organisms. Peroxisomes are also subject to autophagic degradation, a process that involves ATG genes. The interplay between organelle biogenesis and degradation may serve a quality control function, thereby allowing a continuous rejuvenation of the organelle population in the cells
Silicate Clay-Hydrogel Nanoscale Composites for Sustained Delivery of Small Molecules
Hydrogels have been widely used for therapeutic delivery
applications
due to their tunability and biocompatibility, although delivery of
small molecules is difficult due to high burst release and rapid diffusion
from the device. Nanosilicate clays (nanoclays) have shown the adsorption
potential of small molecules, offering a lever to prolong the release
kinetics of hydrogel delivery devices. However, further characterization
of small molecule–nanoclay interactions and their effect on
molecule release is needed to allow for the custom design of tunable
nanocomposite hydrogel delivery devices. Here, we have characterized
the adsorption of small molecules onto three nanoclays, Laponite,
montmorillonite, and halloysite, and monitored their release in various
conditions. The layered structures of Laponite and montmorillonite
led to cationic exchange of the small molecules into the interlayer
space, whereas the small molecules were adsorbed onto the surface
of the tubular halloysite. The addition of nanoclays to polyethylene
glycol (PEG) hydrogels significantly slowed the release of small molecules,
especially from Laponite (500-fold decrease) and montmorillonite (∼3000-fold
decrease) composite gels. Cationic small molecules were shown to be
released significantly slower from nanocomposite hydrogels than anionic
ones. The incubation time of small molecules with nanoclays prior
to hydrogel encapsulation also played a key role in determining their
release rate, with montmorillonite showing near-immediate adsorption
while halloysite exhibited a higher dependence on incubation time
due to slower adsorption kinetics. Release buffer salt concentration
and pH were shown to affect release kinetics due to modulation of
nanoclay–small molecule interactions. These results show the
potential for formation of a highly tunable nanocomposite hydrogel
delivery device for a greatly prolonged release of small molecules
compared to traditional hydrogels