Synthesis and characterization of polymethacrylate-based nitric oxide donors

A synthetic path for the preparation of methacrylic homo- and copolymers containing secondary amine groups that can be converted into nitric oxide (NO) releasing N-diazeniumdiolates is described. The polymers are obtained by a multistep procedure involving synthesis of methacrylate monomers containing boc-protected secondary amine sites, free radical benzoyl peroxide initiated polymerization, deprotection of the amine sites, and subsequent reaction of the polymers with NO in the presence of sodium methoxide. Monomers with both linear and cyclic pendant secondary amines are examined as polymer building blocks. In most cases, polymers are obtained for both types with compositions that agree well with initial monomer ratios and with number average molecular weights (M-n) ranging from 1.69 to 2.58 x 10(6) Da. The final N-diazeniumdiolated methacrylic amine polymers are shown to release NO for extended periods of time with apparent t(1/2) values ranging from 30 to 60 min when suspended in phosphate buffer, pH 7.4. Total NO loading and release for these materials can reach 1.99 mumol per mg of polymer and is proportional to the amine content of the polymer. It is further shown that by using a dimethacrylate cross-linking agent in conjunction with the various methacrylate amines, suspension polymerization methods can be employed to create small (100-200 mum) polymeric methacrylate microbeads. Such microbeads that can be sequentially deprotected and converted to NO release particles via in-situ diazeniumdiolate formation as carried out for the non-crosslinked polymers.