Effect of serum on dose- and temperature-dependent hepatic uptake of multilamellar vesicles(MLV)

Effects of the addition of serum to the perfusate on hepatic uptake of multilamellar vesicles (MLV) were examined in recirculating perfused rat liver. MLV was labelled with both membrane lipid marker ([14C]cholesteryl oleate) and aqueous phase marker ([3H]inulin or 5(6)-carboxyfluorescein (CF)). The uptake rates of [14C]cholesteryl oleate and CF at 37 degrees C coincided well, indicating both markers to be taken up as MLV. Inulin was released from MLV at 37 degrees C but its uptake rate tended to approach that of [14C]cholesteryl oleate at 4 degrees C or at high MLV dose. Some factor in serum promoted MLV uptake at 37 degrees C, but its effect was inhibited at 4 degrees C. The promoting effect was indicated to be possibly due to activation of adsorption of MLV to the hepatic Kupffer cell surface and/or that of phagocytosis by the cells. The saturation of MLV uptake was observed with increase in MLV dose, suggesting the saturation of MLV adsorption to the hepatic cell or the consumption of serum factor which promotes MLV uptake.


Application of synthetic alkyl glycoside vesicles as drug carriers 3 Plasma ccomponents affecting stability of the vesicles


Application of synthetic liposomes based on acyl amino acids or acyl peptides as drug carriers I.Their preparation and transport of glutathione into the liver


Studies on the uptake mechanism of liposomes by perfused rat liver 2.An indispensable factor for liver uptake in serum


Feasibility of magnetic liposomes as a Targeting device for drugs


Studies on the uptake mechanism of liposomes by perfused rat liver 1.An investigation of effuluent profiles with perfusate containing no blood component


Effects of dose and vesicle size on the pharmacokinetics of liposomes


Synthesis and evaluation of a prototypal artificial red cell

A new process allows microencapsulation of purified human hemoglobin and 2,3-diphosphoglycerate to form neohemocytes. The microcapsule membrane is composed of phospholipids and cholesterol. Neohemocytes are substantially smaller than erythrocytes, contain 15.1 grams per decaliter of hemoglobin, and have a P50 value (the partial pressure of oxygen at which the hemoglobin is half-saturated) of 24.0 torr. All rats given 50-percent exchange transfusions survived with only limited evidence of reversible toxicity. Normal serum glutamate-pyruvate-transaminase values at 1, 7, and 30 days after transfusion were consistent with minimal hepatotoxicity. The concentration of blood urea-nitrogen was elevated by 35 percent after 1 day but returned to normal by day 7. However, histopathology revealed normal kidneys on day 1 as well as on days 7 and 30. Neohemocytes cleared from the circulation of transfused rats with an apparent half-life of 5.8 hours.


Tissue distribution and pharmacokinetic evaluation of targeting efficiency of synthetic alkyl glycoside vesicles


Application of synthetic alkyl glycoside vesicles as drug carrier 1.Preparation and physical properties


Correlation between in vivo and in vitro dissolution rates of(a-bromoisovaleryl)urea polymorphs


Pharmacokinetic study on the polymorphs of(a-bromoisovaleryl)urea in rat


The determination of(a-bromoisovaleryl)urea in plasma and the bioavailability of its polymorphic forms in rat


The dissolution properties and physico-chemical properties of polymorphic forms of(a-bromoisovaleryl)urea


The study on the biological fate of pasraben at the dose of practical usage in rat 3.The effect of salicylic acid on the fate of paraben.


The study on the biological fate of paraben at the dose of practical usage in rat 2.The pharmacokinetic study on the blood concentration after the administration of ethyl paraben or p-hydroxybenzoic acid.

The biological fates of ethyl paraben and p-hydroxybenzoic acid in rat were investigated after intravenous and intraduodenal administrations at the dose of 2 mg/kg. The blood concentrations were measured in detail from 3 min after the administration at appropriate time intervals until 90 min. Areas under the blood concentration curves and clearances were calculated from these time course data. Ethyl paraben was little detected in blood after intraduodenal administration. It is suggested that the intestinal metabolism and the first pass effect in liver greatly contribute to the hydrolysis of ethyl paraben. Total radio activity after intraduodenal administration did not show the maximum peak and decreased rapidly. The maximum peak was not observed also in the time course of p-hydroxyhippuric acid after intravenous administration. It shows that not only the rate of hydrolysis but also absorption and conjugation are very rapid. The differences of the areas under the blood concentration curves of p-hydroxybenzoic acid or p-hydroxyhippuric acid was found between the routes or chemical forms of administration. The complex kinetic mechanisms were assumed in the biological fates of these compounds as follows: Conjugation to p-hydroxyhippuric acid is excellent in ethyl paraben administration than p-hydroxybenzoic acid, and in intraduodenal administration than intravenous administration. These phenomenon can not be explained by the conventional kinetic model which is constructed with the connected blood compartments in series. The kinetic models including the assumed routes conjugating directly ethyl paraben in blood or intestine to p-hydroxyhippuric acid were presented, and the least square curve fitting analyses were carried out on these kinetic models.


The preparation and properties of a new polymorphic form of(a-bromoisovaleryl)urea


The study on the biological fate of parabens at the dose of practical usage in rat 1.The metabolism and excretion of etyl p-hydroxybenzoate(ethyl paraben)and p-hydroxybenzoic acid


The pharmacokinetic study on the fate of 8-hydroxyquinoline in rat


A New numerical calculation method for deconvolution in linear compartment analysis of pharmacokinetics