Yoshiyuki Koyama

A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety

Abstract A novel polymer complex system sensitive to glucose was studied as a candidate material for formulating a chemically regulated insulin delivery system. A phenylboronic acid (PBA) moiety was incorporated in poly(N-vinyl-2-pyrrolidone) [poly(NVP-co-PBA) ] as a glucose sensor molecule by the radical copolymerization of N-vinyl-2-pyrrolidone with m-acrylamidophenylboronic acid. Complex formation as well as dissociation was estimated by viscosity changes in the complex solution. A positive viscosity change was observed for the poly (vinyl alcohol) (PVA)/poly(NVP-co-PBA) complex system due to complex formation between PVA diol units and poly(NVP-co-PBA) boronate units; minimal or no change in viscosity was observed for either PVA/boric acid or PVA/poly(NVP). The viscosity of the PVA/poly(NVP-co-PBA) system is able to be controlled through changes in polymer molecular weight and/or polymer concentration. The maximum point in viscosity was observed at a molar ratio of PVA to poly (NVP-co-PBA) of 4:1 in this system. The diol-boronate complex interaction was further investigated by following decreased complex viscosity with the addition of a competitive polyol: glucose, tris(hydroxymethyl)aminomethane (TRIS) or (±)-3-amino-1,2-propanediol (APD). The viscosity decreased steeply when glucose was added while minimal change in viscosity was observed when either TRIS or APD was added. This suggested that the chemical structure of the diol compound had an important role in exchange with the diol-boronate complex. These results point to the promising use of PVA/poly(NVP-co-PBA) complex systems in the development of a novel glucose responsive insulin release system.

Receptor-mediated absorption of high molecular weight dextrans from intestinal tract

Abstract The absorption efficiency of [ 3 H]dextrans from the small intestine evaluated by the in situ closed loop technigue was strongly dose-dependent, and was pronouncedly suppressed by the presence of sugars with structural features similar to those of the reducing end of dextran, such as isomaltose, glucose, and galactose. Isomaltitol, phenyl glucoside and mannose did not affect the dextran absorption. The in vitro permeation study using two chamber-diffusion cells showed that the permeation of [ 3 H]dextran was comparably inhibited by the addition of isomaltose or phlorizin, and also by lowering the temperature from 37°C to 4°C. These results indicate the presence of a specific receptor-mediated mechanism for the intestinal absorption of dextrans.

Radioimmunoimaging of tumors with radioactive antibody against a glycoprotein (GP68) found in developing mouse brain.

SummaryThe in vivo localization of a polyclonal antibody (pAb) against a glycoprotein with a molecular mass of 68 kDa (GP68), which was found in developing mouse brain, was studied in murine tumor models to evaluate potential applications of this antibody for in vivo radioimmunodetection and/or therapy of cancer. The tissue distribution of125I-labeled GP68 pAb 3 days after i.V. injection into mice bearing four different kinds of solid tumor revealed a high uptake ratio by adenocarcinoma 755 and Lewis 3LL lung cancer. In contrast, the uptake ratio was low in mice bearing Ehrlich solid tumor and sarcoma-180 (S-180). These uptake ratios accorded well with the in vitro binding activity of this antibody with the tumor cells. In an immunoscintigraphic study, adenocarcinoma 755 was successfully visualized with67Ga-labeled GP68 pAb. The results of these biodistribution and in vivo radioimmunoscintigraphic studies suggest that GP68 antibody may be applicable to the diagnosis and/or therapy of cancer.