Factors affecting matrix degradation in protein-loaded microgels were investigated for dextran-based microgels, the sugar-binding protein Concanavalin A (ConA), and the dextran-degrading enzyme Dextranase. For this system, effects of enzyme, protein, and glucose concentrations, as well as pH, were considered. Microgel network degradation was monitored by micromanipulator-assisted light microscopy, whereas enzyme and protein distributions were monitored by confocal microscopy. Results show that Dextranase-mediated microgel degradation increased with increasing enzyme concentration, whereas an increased ConA loading in the dextran microgels caused a concentration-dependent decrease in microgel degradation. In the presence of glucose, competitive release of microgel-bound ConA restored the microgel degradation observed in the absence of ConA. To clarify effects of mass transport limitations, microgel degradation was compared to that of non-cross-linked dextran, demonstrating that ConA limits enzyme substrate access in dextran microgels primarily through pore blocking and induction of pore shrinkage. The experimentally observed effects were qualitatively captured by a modified Michaelis-Menten approach for spherical symmetry, in which network blocking by ConA was included. Taken together, the results demonstrate that matrix degradation of protein-loaded microgels depends sensitively on a number of factors, which need to be considered in the use of microgels in biomedical applications.
Lipid nanocapsules
(LNCs) are increasingly being used for various
drug delivery applications due to their versatile nature and ability
to carry a wide variety of therapeutic drug molecules. In the present
investigation, small-angle X-ray (SAXS) and neutron scattering (SANS)
techniques were used to elucidate the structure of LNCs. Overall,
size measurements obtained from SAXS and SANS techniques were complemented
with dynamic light scattering, zeta potential, and cryogenic transmission
electron microscopy measurements. The structural aspects of LNCs can
be affected by drug loading and the properties of the drug. Here,
the impact of drug loading on the overall structure was evaluated
using DF003 as a model drug molecule. LNCs with varying compositions
were prepared using a phase inversion method. Combined analysis of
SAXS and SANS measurements indicated the presence of a core–shell
structure in the LNCs. Further, the drug loading did not alter the
overall core–shell structure of the LNCs. SANS data revealed
that the core size remained unchanged with a radius of 20.0 ±
0.9 nm for unloaded LNCs and 20.2 ± 0.6 nm for drug-loaded LNCs.
Furthermore, interestingly, the shell becomes thicker in an order
of ∼1 nm in presence of the drug compared to the shell thickness
of unloaded LNCs as demonstrated by SAXS data. This can be correlated
with the strong association of hydrophilic DF003 with Kolliphor HS
15, a polyethylene glycol-based surfactant that predominantly makes
up the shell, resulting in a drug-rich hydrated shell.
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