Aim: We analyzed the protein corona of thermoresponsive, poly(N-isopropylacrylamide)- or poly(N-isopropylmethacrylamide)-based nanogels. Materials & methods: Traces of protein corona detected after incubation in human serum were characterized by proteomics and dynamic light scattering in undiluted serum. Results: Apolipoprotein B-100 and albumin were the main components of the protein coronae. For dendritic polyglycerol-poly(N-isopropylacrylamide) nanogels at 37°C, an increase in adsorbed immunoglobulin light chains was detected, followed by partially reversible nanogel aggregation. All nanogels in their hydrophilic state are colloidally stable in serum and bear a dysopsonin-rich protein corona. Conclusion: We observed strong changes in NG stability upon slight alterations in the composition of the protein coronae according to nanogel solvation state. Nanogels in their hydrophilic state possess safe protein coronae.
Thermal magnetic resonance (ThermalMR) accommodates radio frequency (RF)-induced temperature modulation, thermometry, anatomic and functional imaging, and (nano)molecular probing in an integrated RF applicator. This study examines the feasibility of ThermalMR for the controlled release of a model therapeutics from thermoresponsive nanogels using a 7.0-tesla whole-body MR scanner en route to local drug-delivery-based anticancer treatments. The capacity of ThermalMR is demonstrated in a model system involving the release of fluorescein-labeled bovine serum albumin (BSA-FITC, a model therapeutic) from nanometer-scale polymeric networks. These networks contain thermoresponsive polymers that bestow environmental responsiveness to physiologically relevant changes in temperature. The release profile obtained for the reference data derived from a water bath setup used for temperature stimulation is in accordance with the release kinetics deduced from the ThermalMR setup. In conclusion, ThermalMR adds a thermal intervention dimension to an MRI device and provides an ideal testbed for the study of the temperature-induced release of drugs, magnetic resonance (MR) probes, and other agents from thermoresponsive carriers. Integrating diagnostic imaging, temperature intervention, and temperature response control, ThermalMR is conceptually appealing for the study of the role of temperature in biology and disease and for the pursuit of personalized therapeutic drug delivery approaches for better patient care.
Mucosal surfaces pose a challenging environment for efficient drug delivery. Various delivery strategies such as nanoparticles have been employed so far; yet, still yielding limited success. To address the need of efficient transmucosal drug delivery, this report presents the synthesis of novel disulfide‐containing dendritic polyglycerol (dPG)‐based nanogels and their preclinical testing. A bifunctional disulfide‐containing linker is coupled to dPG to act as a macromolecular crosslinker for poly‐N‐isopropylacrylamide (PNIPAM) and poly‐N‐isopropylmethacrylamide (PNIPMAM) in a precipitation polymerization process. A systematic analysis of the polymerization reveals the importance of a careful polymer choice to yield mucus‐degradable nanogels with diameters between 100 and 200 nm, low polydispersity, and intact disulfide linkers. Absorption studies in porcine intestinal tissue and human bronchial epithelial models demonstrate that disulfide‐containing nanogels are highly efficient in overcoming mucosal barriers. The nanogels efficiently degrade and deliver the anti‐inflammatory biomacromolecule etanercept into epithelial tissues yielding local anti‐inflammatory effects. Over the course of this work, several problems are encountered due to a limited availability of valid test systems for mucosal drug‐delivery systems. Hence, this study also emphasizes how critical a combined and multifaceted approach is for the preclinical testing of mucosal drug‐delivery systems, discusses potential pitfalls, and provides suggestions for solutions.
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