ENZYMATIC DEGRADATION OF POLY(ETHYLENE GLYCOL) MODIFIED DEXTRANS

Poly(ethylene glycol) (PEG), with molecular weight 2,000 and 5,100, were conjugated to dextran (T-40) with three different degrees of substitution. The biodegradation of the six PEG-dextran conjugates was evaluated, using dextranase, isolated rat cecum cell free extracts (CFE), and rat liver lysosomal enzymes. All the substrates were degraded by dextranase; however, the rate of the degradation decreased with an increase in the degree of modification as well as in the molecular weight of PEG. When incubated with CFE, these conjugates were degraded with reduced rates, but a similar trend was observed, indicating the presence of an endo-acting dextranase in the rat cecum contents. The modified dextrans, however, resisted degradation by lysosomal enzymes in vitro during 36 h incubation at 37-degrees-C. The degradation of modified dextrans was evaluated by gel permeation chromatography (GPC). For the degradation of dextran conjugates by dextranase, two additional methods were also employed, i.e., static light scattering (SLS), and dynamic light scattering (DLS). The results, as compared to those published on the modification of dextrans with low molecular weight reagents, demonstrated the PEGs' unique effects on the interaction of modified substrates with proteins. It appears that PEG conjugation reduced the enzymatic degradability of dextran conjugates not only due to the modification of dextran structure and the sterical hindrance to the formation of the enzyme-substrate complex, but also by the participation of PEG chains in the repulsion of enzyme molecules.