CONTROLLED-RELEASE OF MACROMOLECULES FROM A DEGRADABLE POLYANHYDRIDE MATRIX

Polymeric matrices that slowly release macromolecules may be useful for the controlled delivery of proteins or polymer-drug conjugates for targeted drug delivery. Solid particles of fluorescein and fluorescently-labeled, size-fractionated dextran (4000-150 000 number average molecular weight) were dispersed in degradable polyanhydride matrices composed of a 1 : 1 copolymer of fatty acid dimers and sebacic acid. The release of macromolecules from the polymer matrix into buffered saline was measured; changes in the polymer during immersion were monitored by infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Although significant hydrolysis of the polymer occurred within the first day, the matrices remained intact and water-soluble tracers were slowly released for several days. During polymer hydrolysis and erosion, micron-sized pores developed throughout the 2 mm thick polymer matrix, permitting water penetration into the matrix and tracer diffusion out of the matrix. The rate of tracer release from the matrix depended on tracer particle size; rates of fluorescein isothiocyanate dextran release were controlled by adjusting the size of particles dispersed in the matrix.