CONTROLLED-RELEASE OF MACROMOLECULES FROM A DEGRADABLE POLYANHYDRIDE MATRIX

Polymeric matrices that slowly release macromolecules may be useful fo r the controlled delivery of proteins or polymer-drug conjugates for t argeted drug delivery. Solid particles of fluorescein and fluorescentl y-labeled, size-fractionated dextran (4000-150 000 number average mole cular weight) were dispersed in degradable polyanhydride matrices comp osed of a 1 : 1 copolymer of fatty acid dimers and sebacic acid. The r elease of macromolecules from the polymer matrix into buffered saline was measured; changes in the polymer during immersion were monitored b y infrared spectroscopy, differential scanning calorimetry, and scanni ng 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 fr om the matrix depended on tracer particle size; rates of fluorescein i sothiocyanate dextran release were controlled by adjusting the size of particles dispersed in the matrix.