(765e) Nanoscale Anionic Hydrogel Prepared by Emulsion Polymerization for Oral Delivery of siRNA
Introduction: Design parameters of an effective oral delivery vehicle for small interfering RNA (siRNA) include traversing the digestive tract then crossing the cell membrane into the cytosol, all while maintaining the bioactivity of the easily-degraded siRNA. Anionic hydrogels have been shown to have suitable properties for oral delivery of delicate proteins1, 2, and may also be useful as part of composite carrier system to deliver encapsulated siRNA to the site of cell uptake. The aim of this work was the development of a novel emulsion photopolymerization to synthesize hydrophilic, pH-responsive anionic hydrogels which can be incorporated into a composite carrier for the oral delivery of siRNA to the gastrointestinal tract.
Materials and Methods: The monomers N-vinylpyrrolidone (NVP), methacrylic acid (MAA), and crosslinking agent poly(ethylene glycol) dimethacrylate 400 (PEGDMA400) were polymerized in a water-in-oil (WO) emulsion using photo-initiator Irgacure®184 (1-hydroxy-cyclohexyl-phenylketone). Emulsion stability and resultant particle properties were tuned by varying surfactants, surfactant ratios, and the degree of neutralization of MAA. A UV/VIS absorbance microplate reader was used to screen emulsion stability. Dynamic light scattering (DLS) was used to measure particle size and zeta potential in phosphate buffered saline from pH values of 3.2 to 7.2. Scanning electron microscopy (SEM) was also used to evaluate the stability of the emulsion by the size distribution and morphology of the particles.
Results and Discussion:An optimal co-surfactant system and WO emulsion compositions were determined to achieve a stable photoemulsion polymerization for synthesis of hydrophilic P(MAA-co-NVP) hydrogel particles. The size distribution and morphology of the particles can be tailored by adjusting the co-surfactant ratios and the amount of surfactant in the emulsion, as shown in DLS and SEM. The pH-response and zeta potential of the polymer indicate that it is a suitable material to be used in the composite hydrogel system for oral delivery of siRNA. We are proceeding with encapsulation of a secondary hydrogel material to form the composite oral delivery system.
Acknowledgements: This work was supported by a National Science Foundation grant (CBET 10-33746) and a NSF Graduate Fellowship to JMK.
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