Keizo Shida

Fusibility of Poly(N-carboxy α-Amino Acid Anhydride) Materials Treated under Pressure-Heat Conditions and in Vitro-in Vivo Degradation of Hot-Pressed Materials

Abstract Powdered poly(N-carboxy α-amino acid anhydride) materials were treated at temperatures of 50, 100, 150, and 200°C under a pressure of 150 kg/cm2. A number of hot-pressed materials showed simultaneous fusion and contraction in volume. The fusion temperature of the hot-pressed materials was generally lower than the true melting point of the powdered materials at atmospheric pressure (determined with a Differential Scanning Calorimeter). The hot-pressed materials had high rigidity and transparency. The in vitro-in vivo degradation of hot-pressed materials was also investigated. The homo- and copoly(α-amino acid) materials used in this study were scarcely degraded, though debenzylated t e rpolymers such as β-benzyl-L-aspartate/aspartic acid/L-leucine and γ -benzyl-L- glutamate/glutamic acid/L - leucine we re significantly degraded in both the in vitro and in vivo experiments. It was found that the in vivo degradation profile of hot-pressed terpolymer materials corresponds relatively well to degradati...

In vivo release of testosterone from vinyl polymer composites prepared by radiation-induced polymerization

Polymer-testosterone composites with long periods of controlled slow release were made by radiation-induced polymerization in a supercooled state at low temperature using glass-forming monomers. The in vitro release of testosterone from various vinyl polymer composites was found to follow a matrix-controlled process (Q-t1/2). The rate of drug delivery was accelerated with increasing water content of polymers. In experiments in vivo, the composites were implanted subcutaneously in the back of castrated rats during the 30 day test period. The in vivo release rate of testosterone was a little smaller than in vitro. This difference between two releases also increased with the increase of hydrophilicity of polymer. The physiological response in rats was investigated by measuring the weight of ventral prostate and serum testosterone concentration with testosterone-containing composites. The weight of ventral prostate increased linearly with increasing rate of drug release and the serum testosterone concentration could be correlated with the release and with the weight increase of ventral prostate. It was found from microscopic observation that the used polymer carriers had relatively good biocompatibility to cause little foreign body reaction.

In vivo release of testosterone from protein-vinyl polymer composites

Hydrophilic vinyl polymer-protein composites containing testosterone were made by means of thermal denaturation of albumin after radiation-induced polymerization of 2-hydroxyethylmethacrylate (HEMA) at--78 degrees C. The albumin-HEMA mixed polymer can be considerably digested with trypsin. The degree of digestion was smaller than that expected from calculation. It was deduced that the digestion of the albumin component was retarded in the presence of HEMA. The same tendency was observed in in vivo experiments. At the same time, in vivo release of testosterone was depressed in albumin-HEMA mixed polymer composite in accordance with the weight decrease of polymer composite resulting from digestion. The effect of testosterone on the weight of ventral prostate was investigated using composites in castrated Wistar rats. The effect was larger in the controlled slow release from implanted composites rather than that of dosage by injection. The microscopic observation showed that the inflammation and foreign body reaction in rat tissue were retarded in albumin-HEMA mixture polymer composite compared with 100% albumin composite.