Deamidation of a model hexapeptide in poly(vinyl alcohol) hydrogels and xerogels

Polymeric controlled release systems have been proposed to prolong the half-lives of protein and peptide drugs in vivo and to deliver active drug at a controlled rate. These systems are ineffective, however, if the drug is not stable during storage and release. This study addresses the effect of poly(vinyl alcohol) on the stability and release of an incorporated hexapeptide, VYPNGA, which undergoes deamidation. Two types of peptide-loaded poly(vinyl alcohol) matrices were formed, a semisolid hydrogel and a lower water content 'xerogel', and stored at 50 degrees C for up to 122 days. The hexapeptide was less stable in both poly(vinyl alcohol) matrices than in aqueous buffer or lyophilized polymer-free powders. The type of poly(vinyl alcohol) matrix appeared to influence the degradation mechanism, since the product distributions differ in the hydrogel and the xerogel. The results suggest that, rather than stabilizing this peptide, incorporation in poly(vinyl alcohol) matrices reduces stability relative to solution and lyophilized controls.