Combinatorial/high throughput methods for the determination of polyanhydride phase behavior.

Combinatorial methods have been developed to study the phase behavior of biodegradable polyanhydrides for drug delivery applications. The polyanhydrides of interest are poly[1,6-bis(p-carboxyphenoxy) hexane] (CPH) and poly[sebacic anhydride] (SA). Both continuous and discrete polymer blend libraries were fabricated by using a combination of solution-based gradient deposition and rapid prototyping. Blend compositions were characterized via a high throughput transmission Fourier transform infrared (FTIR) sampling technique and compared against theoretical mass balance predictions. To obtain phase diagrams of CPH/SA, the effect of blend composition and annealing temperature on the miscibility of the blend was studied. This gradient library was observed with optical microscopy in order to determine cloud points. These results were compared with a theoretical phase diagram obtained from Flory-Huggins theory and with atomic force microscopy (AFM) experiments on blend libraries and the agreement between the methods was very good. The high throughput method demonstrates that the CPH/SA system exhibits upper critical solution temperature behavior. These libraries are amenable to other high throughput applications in biomaterials science including cell viability, cell activation, and protein/biomaterial interactions.