(626e) Design of pH-Responsive Hydrogels for Oral Delivery of High Isoelectric Point Therapeutic Proteins
Copolymeric nanoparticle systems containing itaconic acid (poly(itaconic acid-grafted-poly(ethylene glycol)) and poly(itaconic acid-co-N-vinylpyrrolidone)) and crosslinked with tetraethylene glycol dimethacrylate were synthesized via UV-initiated free radical emulsion polymerization. Following purification, the composition of the resulting particles was confirmed with Fourier-transform infrared spectroscopy, nuclear magnetic resonance, potentiometric titration, and differential scanning calorimetry. The surface morphology of the nanogels was evaluated using electron microscopy. Nanogel swelling was characterized with dynamic light scattering and the zeta potential was measured with electrophoretic light scattering. Loading and release studies of high pI proteins were conducted in physiologically relevant buffers and quantified with a microBCA assay. The nanogels were confirmed to have the expected conformation, morphology, and properties. The itaconic acid-based platforms exhibited a greater degree of swelling than the methacrylic acid-based systems. Both platforms successfully loaded high pI protein from solution before collapse was induced by reducing the pH to simulate gastric conditions. Upon raising the pH to simulate intestinal conditions, a larger fraction of protein was released from the itaconic acid-based particles than the methacrylic acid-based system.
This work was supported in part by NIH grant number R01 EB022025 and an NSF GRF.
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