THE PHYSICOCHEMICAL AND BIOPHARMACEUTICAL PROPERTIES OF FRAGMENTED KERATIN AS A NEW DRUG CARRIER

Two types of fragmented keratin were prepared from buffalo horn and ho of using savinase and Na2S, and their physicochemical and biopharmaceu tical properties mere examined in mice. The number-average molecular w eight of enzymatically fragmented keratin (E-FK), chemically fragmente d keratin (C-FK), and fragmented gelatin (FG) were 8000, 33000, and 66 00, respectively. The systematic acute toxicity of FKs was significant ly low. Moreover, the immunogenicity of FKs was significantly lower th an that of superoxide dismutase. FKs and FG were partially hydrolyzed by trypsin. FKs were digested easily by alpha-chymotrypsin, but FG und erwent less hydrolysis under the same conditions. FKs were bound to pl asma proteins, including albumin, and also to some proteins in liver a nd kidney homogenates. In plasma, E-FK was hydrolyzed slowly, but in l iver and kidney homogenates it showed slightly faster hydrolysis. In c ontrast, FG was not hydrolyzed in any of the media used here. After in travenous administration of FKs and FG to mice, these molecules were r apidly eliminated from the plasma. E-FK and C-FK were taken up into th e kidneys (CL(uptake, kidney),; 10400, 11600 mu l/h/g), and then gradu ally excreted in urine. FG was excreted rapidly into urine (CL(urine); 6360 mu l/h). Interestingly, C-FK was also taken up into the liver (C L(liver); 4820 mu l/h). These results indicated that fragmented kerati ns are biodegradable materials and might be used as new types of liver - and kidney-specific targeting carriers.