Sadao Hirota

Effects of glycophorin and ganglioside GM3 on the blood circulation and tissue distribution of liposomes in rats

Abstract The effects of glycophorin (GP) and ganglioside GM 3 (GM 3 ) on the blood circulation and tissue distribution of liposomes were investigated in rats. Liposomes composed of dipalmitoylphosphatidylcholine (DPPC)/cholesterol (Chol) or sphingomyelin (SM)/Chol, which contained additionally GP and/or GM 3 , were prepared and the blood concentration and tissue (liver, kidney, lung and spleen) distribution after intravenous administration were compared with the control liposomes which contained neither GP nor GM 3 . The blood concentration of DPPC liposomes containing GP and GM 3 (GP-GM 3 -Lip[DPPC]) was significantly higher than those of the other DPPC liposomes for up to 6 h after administration, and about 3.3-fold higher than that of control liposomes (Con-Lip[DPPC]) at 6 h. The liver uptake of GP-GM 3 -Lip[DPPC] at 6 h was significantly reduced compared with that of Con-Lip[DPPC], while the spleen uptake was increased significantly. Similarly, in the case of SM liposomes, the liposomes containing GP and GM 3 (GP-GM 3 -Lip[SM]) prolonged the blood circulation time of liposomes and reduced their uptake by the liver, and the blood concentration was about 3.7-fold higher than that of control liposomes (Con-Lip[SM]) at 6 h. It was found that GP and GM 3 were useful and valuable for prolonging the blood circulation time of liposomes and reducing the uptake of liposomes by the liver.

STUDIES ON TECHNIQUES FOR INTRACELLULAR INTRODUCTION OF MACROMOLECULES

Publisher Summary This chapter discusses the use of the silkworm Bombyx mori nuclear polyhedrosis virus (BmNPV) system for the hyperproduction of ts-src, v-myc, v-erbB, and v-sis products as a fusion protein with the viral protein polyhedrin (NP). Fluoresceinisothiocyanate (FITC)-bovine serum albumin (BSA) and FITC-dextran are used as markers, and these markers are introduced into L cells in high frequency with improved liposome techniques. Chimeric oncogenes with the polyhedrin gene of BmNPV can be highly expressed as fused proteins. In case of v-src and v-erbB genes, their products show tyrosine kinase activity even in a fused form. Purification of the products seems to be a little bit difficult as they are insoluble in water. Cleavage of the domain of the oncogene from a fused protein and its purification without loss of biological function remains to be solved. The chapter describes the effort to improve the liposome methods and presents the development of new methods with which constant and high efficiency introduction can be obtained.

Texture Study on Optimum Formulation of Molded Poultices

In the previous paper, the value (xi) of the ith physical property of a molded poultice was measured, the preference value (yj) for the jth textural characteristic was obtained in sensory tests, and a mathematical expression for the relation between yj and xi was obtained in the form of first-order regression equations with good regression coefficients. A study was performed to ascertain whether xi is related to and can be obtained from the quantities, ak, of components, k, in a preparation. Molded poultices of 53 formulations contaning various quantities of nine ingredients were prepared and their physical properties were measured. For seven of their properties, the relations between xi and ak were analyzed by stepwise multiple regression analysis and were obtained in the form of first-order regression equations with a confidence level above 95%. These relations made it possible to carry out simulation of the optimum formulations of molded poultices.One of the simulated optimum formulations showed viscoelasticity at 50°C obeying the four-element model, whose values were dete mined from creep test data.

Dielectric Studies of Emulsions of Polyol in Hydrophobic Colloidal Silica-Oil Gel

The dielectric relaxation due to the interfacial polarization of emulsions of either polyol or aqueous solutions of polyol in a hydrophobic colloidal silica-oil gel (P/(S·O) emulsions) was investigated over a wide range of volume fractions of the dispersed phase at frequencies ranging from 10 kHz to 3MHz. P/(S·O) emulsions without surfactant showed dielectric relaxation, and the limiting dielectric constants at high and low frequencies, eh, el, limiting dielectric conductivity at high frequency, Kh, and relaxation frequency, fo, were shown to satisfy the equations given by Wagners theory4) up to a dispersed phase fraction as high as 0.6. In P/(S·O) emulsions without surfactant, the absence of any particle aggregation was ascertained by microscopic observation. When the polyol was diglycerin, several dispersed phases with different dielectric constants were obtained at different mixing ratios of water and diglycerin. It was found that the values of el changed markedly on the addition of surfactant, increasing as the dielectric constant of the dispersed phase, ep, became larger. In P/(S·O) emulsions with surfactant, particle aggregation was found by microscopic observation. The fo values of P/(S·O) emulsions with particle aggregation were smaller than in those without particle aggregation, in spite of the increase in electric conductivity of the dispersed phase brought about by the addition of a surfactant. It should be noted that the magnitude of the dielectric anomaly1) varies with the magnitude of ep even if the added amount of surfactant is the same.