We recently developed the synthesis of the first polysulfenamides, polydiaminosulfides, and polydisulfidediamines and have investigated their ability to deliver drugs. Prior to our work, the sulfenamide (R2NSR), diaminosulfide (R2NSNR2), and disulfidediamine (R2NSSNR2) functional groups were not used in the synthesis of polymers. We developed simple methods to synthesize each of these polymers and studied their stabilities in organic solvents and water at different pH values. These polymers were all stable in organic solvents, but they slowly degraded over hours in water at neutral pH and within minutes in water at a pH of 5. The degradation of each of these functional groups was at least two orders of magnitude faster under acidic conditions than the degradation of esters which are commonly used in drug delivery. Microparticles were fabricated from these polymers and studied for their ability to be loaded with dyes and for how fast they released the encapsulated dyes in water.  Furthermore, the toxicity of these polymers were studied in in vitro experiments in HEK-293 cells and in vivo experiments in mice. Importantly, no evidence of any toxicity was observed which is notable for three news sets of polymers. The products of degradation of each set of polymers was investigated. The sulfenamides degraded to release sulfenic acids that rapidly dimerized to yield thiosulfinates. Thiosulfinates are the same functional group found in allicin which is a component of garlic and believed to be responsible for the excellent antioxidant properties of garlic. The diaminosulfides degraded to release sulfur monoxide while the disulfidediamines degraded to release hydrogen sulfide. Each of these functional groups have unique stabilities and products of degradation that can be used to optimize their properties in vivo.

Synthesis of polymers based on sulfur-nitrogen bonds for drug delivery

246th National Meeting (2013)

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