Masayuki Nakagaki

Stabilization of the lamellar structure of phosphatidylcholine by complex formation with trehalose

Abstract Trehalose (Tre) is found at particularly high concentration in anhydrobiotic organisms, and is effective in stabilizing the bilayer membranes of phospholipids in freeze-drying. We studied the mixture of L -α-dipalmitoylphosphatidylcholine (DPPC) and trehalose at various water contents by differential scanning calorimetry (DSC) and the small angle X-ray diffraction method. The Tre intercalated between lipid bilayers and formed complexes, and the excess Tre crystallized as its dihydrate by the addition of water. The amount of the dihydrate was estimated from the peak area in DSC. The experimental values of the molar ratio (Tre/DPPC) of the complexes thus determined were 1:2 and 1:1, and the corresponding expansions of the lamellar spacing were observed by small angle X-ray diffraction.

Membrane potential of separation membranes as affected by ion adsorption

Abstract Recently it has been reported that membrane charge density depends on the bulk concentration. In this paper, we investigate the effect of ion adsorption on membrane charge and on membrane potential by using the selective ion adsorption model, which considers that a membrane which has no fixed charge can adsorb anions selectively. We find that the membrane potential depends on the bulk concentration as if the membrane itself had a fixed charge. However, the magnitude of the membrane potential in the region of low bulk concentration is determined by the adsorption coefficient and the saturated ion concentration of adsorbed ions. These parameters can be determined by analysis of the membrane potential using our model. After obtaining values of parameters which characterize the membrane, the variation of the membrane charge density and the interfacial potential difference caused by ion adsorption can be predicted theoretically.

Influence of bile salts on the permeability of insulin through the nasal mucosa of rabbits in comparison with dextran derivatives

Abstract Nasal drug absorption and the effect of absorption promoters have been studied in rabbits. Nasal mucosa excised from rabbits was mounted as a flat sheet in an in vitro chamber. The increase in the membrane permeability coefficient for sodium chloride indicates the change in the porosity by pretreatment with bile salts. The permeabilities for dextran derivatives were enhanced by pretreatment with sodium glycocholate (GC). The permeability coefficient (P) for fluorescein isothiocyanate diethylaminoethyl dextran (FITC DEAE-dextran, DE) was higher than that for FITC-dextran (DT), and P for FITC dextran sulfate (DS) was lower than that for DT with the same molecular weight. Comparing insulin with dextran of the same molecular weight as insulin, the value of P for insulin induced by pretreatment with GC was higher than that for hydrophilic dextran. The partition coefficient seemed to have much more effect on the nasal membrane transport than the molecular weight of the penetrant.

Theoretical study of the effect of ion adsorption on membrane potential and its application to collodion membranes

Abstract Charged membranes have been characterized by many investigators. Their attention has mostly focussed on the fixed charge of uniform membranes, but in recent years it has been pointed out that real membranes are not perfectly homogeneous. In this paper, the effect of selective ion adsorption on the membrane potential has been investigated theoretically in order to find a suitable model for a real membrane. The membrane considered here is, for simplicity, one which has a positive fixed charge and adsorbs anions selectively. As a result, it is found that the membrane potential shows a minimum with the decrease of bulk concentration. This phenomenon, which results from changes in the effective membrane charge density, is due to the variation of the amount of ions adsorbed by the membrane. The theory is applied to the analysis of the membrane potential of a collodion membrane, and it is shown that the theory is in good agreement with experimental data. Our model is adequate for obtaining information on the fixed membrane charge density, the saturated amount of adsorbed ion and the adsorption coefficient by the analysis of the membrane potential. The positive deviation of the products of the partition coefficients of co-ion and counter-ion for the membrane charge is well explained by the model.

Determination of the acid dissociation constants in ethanol-water mixtures and partition coefficients for diclofenac

Abstract The dissociation constants of diclofenac in ethanol-water mixtures, in connection with percutaneous absorption, were determined using the titration method. The acid dissociation constant of sodium diclofenac was decreased by the increase in the concentration of ethanol in the aqueous solution. The results were interpreted in terms of solvent polarity. It is suggested that ethanol, which is used as an enhancer for percutaneous absorption, assumes another role, increasing the proportion of the unionized form of the drug and forming ion pairs in low dielectric media. Also the partition coefficients for diclofenac were measured in an n-octanol/water or buffer system over the pH range from 3 to 8. The distribution behavior of diclofenac is dramatically affected in the presence of added cations. Above pH 7, ion pair formation promotes the distribution of the drug into lipophilic environment.

Influence of Bile Salts on the Permeability Through the Nasal Mucosa of Rabbits of Insulin in Comparison with Dextran Derivatives

The nasal drug absorption and the effect of absorption promoters have been studied in rabbits. Nasal mucosa excised from rabbits was mounted as a flat sheet in an in vitro chamber. The result indicates that the change in the porosity of the membrane by pretreatment with bile salts increased the permeability coefficient of sodium chloride in the nasal membrane. The permeabilities of dextran derivatives were enhanced by pretreatment with sodium glycocholate (GC). The permeability coefficient (P) of fluorescein isothiocyanate diethylaminoethyl dextran