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(742c) Alginate Nanoparticle Platform for Controlled Release of Biotherapeutics

Authors: 
Vela Ramirez, J., UT Austin
Peppas, N. A., University of Texas at Austin
Barrios Santos, D., University of Texas at Austin
The design of novel drug delivery vehicles has been focused on the synthesis and development of materials that can load and release biomolecules for therapeutic or prophylactic use with a controlled behavior. These materials need to be biocompatible, and depending on their application stimulate the immune system appropriately. Alginates are anionic polymers that have been used for drug delivery and tissue regeneration since they are bioresorbable and non-immunogenic. These materials can be ionically or chemically crosslinked, creating different physicochemical characteristics. This ability is critical to tailor the properties of alginate-based drug delivery vehicles. By combining ionic and chemical crosslinking methods on alginate nanoparticles the release profiles of biotherapeutics can be modified to develop platforms with sustained delivery mechanisms.

The studies described herein were developed to synthesize a drug delivery platform based on alginate nanoparticles using dual crosslinking mechanisms. Sodium alginate was functionalized with methacrylic anhydride via the esterification of its hydroxyl groups. Successful functionalization of alginate was confirmed via Fourier transform infrared spectroscopy and NMR spectroscopy. Alginate nanoparticles were synthesized using water-in-oil microemulsions. Briefly, a functionalized-alginate solution (up to 15% (v/v)) was emulsified in toluene with the biomolecule, 1% (w/w) Span80® as a surfactant, and 1% (w/w) Irgacure 2959 as a photoinitiator. Nanoparticle solutions were then crosslinked for various times using a UV point-source at 140 mW/cm2. Resulting nanoparticles were purified and then suspended in a calcium chloride solution (5M) over different periods of time. Particle characterization was performed using light and electron microscopy, dynamic light scattering and zeta potential measurements confirming the morphology and charge of the functionalized alginate nanoparticles. Most importantly, the ability of these nanoformulations to release proteins with a sustained release profile were evaluated. The release profile of three different proteins with either similar molecular weights or isoelectric points were analyzed under solutions with decreasing levels of ionic groups. The degree of chemical crosslinking combined with the molar concentration of the ionic solution affected the release profiles of the protein molecules. These results show that combination of different crosslinking methodologies can confer natural polymer systems, such as alginate nanoparticles, the ability to be delivery vehicles for biotherapeutics with controlled release behaviors.