Yoh-ichi Matsushita

Liposomal heme as oxygen carrier under semiphysiological condition

Abstract To prepare a potent synthetic oxygen carrier in aqueous media, the iron(II) picket fence porphyrin complex with one hydrophobic imidazole was incorporated into a lipid bilayer of phosphatidylcholine. The incorporation was confirmed by gel permeation chromatography and ultracentrifugation, which indicates the complex being trapped in the multilayer liposome. The liposomal iron(II) porphyrin complex could bind molecular oxygen reversibly in neutral aqueous media and in the serum of a rat blood at 25°C.

Polymerizable glycerophosphocholines containing terminal 2,4-hexadienyloxy groups and their polymerized vesicles(1)

SummaryPolymerizable glycerophosphocholines containing one or two 2,4-hexadienyloxy groups at the terminal of the acyl chains were prepared. Those were 1-[11-(2,4-hexadienyloxy)undecanoyl]-2-0-alkyl-rac-glycero-3-phosphocholines 1, 1-acyl-2-[11-(2,4-hexadienyloxy)undecanoyl]-sn-glycero-3-phosphocholines 2 and 1,2-bis[11-(2,4-hexadienyloxy)undecanoyl]-sn-glycero-3-phosphocholine 3. Those having one hexadienyloxy group formed small unilamellar vesicles. One having two groups formed lipid bilayers, but not unilamellar vesicles. 1 and 2 could form stable microcapsules (polymerized vesicles) with the diameters ranging from 20 to 40 nm.

Enzymatic reduction of synthetic hemin to heme and its application to study on oxygenation in aqueous medium

Abstract The enzyme system consisting of glucose-6-phosphate, glucose-6-phosphate dehydrogenase, ferredoxin, ferredoxin-NADP-reductase, and NADP was used to reduce various synthetic iron(III) porphyrins to iron(II) in aqueous buffer (pH7.0) at 25°C. The oxygenation reactions of the thus prepared iron(II) porphyrin complexes were examined and it was found that only the iron(II) picket fence porphyrin-mono(1-lauryl-2-methylimidazole) complex incorporated in liposomes of phosphatidylcholine can form a stable oxygen adduct at 25°C in neutral aqueous medium.

Interaction of Oxygen Carrying Microparticles with Blood Components and Clearance from Blood Stream

The stable microparticles (polymeric liposomes) having a synthetic heme-imidazole complex and carrying oxygen were studied in the interaction with blood components in vitro. They did not induce hemolysis, platelet aggregation and plasma coagulation directly and were stable against the hydrolysis by phospholipases. Intravenous injection of the 14C-labeled particles into rats indicated the half-disappearance time from the blood stream of ca. 14 hr. Their tissue distribution was analyzed with time by autoradiography.The authors have demonstrated that a stable synthetic oxygen carrier can be prepared by embedding a synthetic heme complex into the hydrophobic region of lipid bilayers of liposomes (1–4). By the use of polymeric liposomes (5), we have succeeded in preparing a stable solution of high heme concentration (6). The new oxygen-carrying aqueous solution had physical properties similar to those of whole blood. To elucidate the further possibility of the micro-particles as red blood cell models, the inte...