The physicochemical and biopharmaceutical properties of fragmented keratin as a new drug carrier

Abstract

Two types of fragmented keratin were prepared from buffalo horn and hoof using savinase and Na2S, and their physicochemical and biopharmaceutical properties were examined in mice. The number-average molecular weight of enzymatically fragmented keratin (E-FK), chemically fragmented keratin (C- FK), and fragmented gelatin (FG) were 8000, 33000, and 6600, respectively. The systematic acute toxicity of FKs was significantly low. Moreover, the immunogenicity of FKs was significantly lower than that of superoxide dismutase. FKs and FG were partially hydrolyzed by trypsin. FKs were digested easily by α-chymotrypsin, but FG underwent less hydrolysis under the same conditions. FKs were bound to plasma proteins, including albumin, and also to some proteins in liver and kidney homogenates. In plasma, E-FK was hydrolyzed slowly, but in liver and kidney homogenates it showed slightly faster hydrolysis. In contrast, FG was not hydrolyzed in any of the media used here. After intravenous administration of FKs and FG to mice, these molecules were rapidly eliminated from the plasma. E-FK and C-FK were taken up into the kidneys (CL(uptake, kidney); 10400, 11600 μl/h/g), and then gradually excreted in urine. FG was excreted rapidly into urine (CL(urine); 6360 μl/h). Interestingly, C-FK was also taken up into the liver (CL(liver); 4820 μl/h). These results indicated that fragmented keratins are biodegradable materials and might be used as new types of liver- and kidney-specific targeting carriers.