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