BIODEGRADATION OF POLY(AMINO ACID)S - EVALUATION METHODS AND STRUCTURE-TO-FUNCTION RELATIONSHIPS

Two poly(amino acid) systems were studied. (a) poly[N-5-(2-hydroxyethy l)-L-glutamine] (PHEG) derivatives prepared by NCA polymerization; (b) oly-alpha,beta-[N-(2-hydroxyethyl)-DL-aspartamide] (PHEA) derivatives prepared by thermal polycondensation of aspartic acid to racemic poly succinimide followed by chemical modification reactions. The degradati on of polymers by isolated enzymes and homogenate of kidney tissue was studied in vitro and the effect of polymer structure on the rare of d egradation and the size of degradation products was evaluated. A PHEA derivative (modified by tyramine residues in 9.6% of side chains) was accumulated in the lysosomes of kidney cells of rats and the molecular -weight distribution of the polymer retained inside the lysosomes of l iving cells and that of the polymer excreted into urine was analysed b y a high sensitivity size-exclusion chromatography using the fluoresce nce and radioactive labelling While PHEG derivatives were degraded by isolated mammalian enzymes and a tissue homogenate, no significant deg radation of PHEA and derivatives was observed, either in vitro, with i solated enzymes and homogenate or in vivo, under a long-term exposure to the lysosomal enzymes in living cells.