Poly(butanediol spermate): A hydrolytically labile polyester-based nitric oxide carrier

A polyester composed of spermic acid and 1,4-butanediol was synthesized via a Michael-type reaction, using 1,4-diaminobutane and 1,4-butanediol diacry late. A linear polymer, poly(butanediol spermate), with Mw of 3,000 and a m olecular weight distribution of 1.95, was insoluble in organic solvents, bu t slowly dissolved in water. After dissolving in water poly(butanediol sper mate) hydrolyzed to produce spermic acid and 1,4-butanediol. The rate of hy drolysis was pi-I-dependent. At 20 degrees C in buffers of pH 9.7, 7.4, and 4.8, 50% decomposition occurred in 2.5, 1.5, and 3.5 hours, respectively. Secondary amines in the polymer were chemically modified (34-45%) with nitr ic oxide to form 1-substituted diazen-1-ium-1,2-diolates which spontaneousl y released nitric oxide in neutral or acidic aqueous solutions. The poly(bu tanediol spermate) diazeniumdiolate, in pH 7.4 buffer at 37 degrees C, slow ly dissolved and hydrolyzed with a 50% hydrolysis in 190 hours. Nitric oxid e release from the polymer was delayed for approximately 100 hours then giv en a first order release of nitric oxide with a half-life of 110 hours. In contrast, at pH 5.0 and 37 degrees C, the poly(butanediol spermate) diazeni umdiolate slowly dissolved but immediately released nitric oxide with a hal f-life of 180 hours, and 50% hydrolysis time for polymer of 520 hours. Poly (butanediol spermate) diazeniumdiolate is potentially useful for site-speci fic nitric oxide delivery with subsequent hydrolysis of polymer to natural products when used in mildly acidic to neutral conditions.