Toru Takagishi

Novel pH-sensitive liposomes: liposomes bearing a poly(ethylene glycol) derivative with carboxyl groups

Three kinds of succinylated poly(glycidol)s were synthesized as poly(ethylene glycol) derivatives having carboxyl groups by the reaction of poly(glycidol) with varying amounts of succinic anhydride in dimethylformamide. These polymers promoted fusion of egg-yolk phosphatidylcholine liposome more intensively with decreasing content of carboxyl groups at pH 7.4, although the extent of fusion was limited. However, the polymer with 56% of succinylated residues induced fusion of the liposome much more strongly at pH 4.0. Egg-yolk phosphatidylcholine liposomes bearing the succinylated poly(glycidol) which was combined with long alkyl chains as anchors to the liposomal membrane were prepared. The leakage of calcein entrapped in the inner aqueous phase of the liposomes was slight at pH 7.4. However, the leakage increased with decreasing pH. The turbidity measurement and the fusion assay indicate that the liposomes bearing the polymer fuse more intensively with decreasing pH and with increasing amount of the polymer bound to the liposomes.

Permeability characteristic of polyelectrolyte complex capsule membranes: Effect of preparation condition on permeability

Because polyelectrolyte complex formation is known to depend on charge densities of polyelectrolytes, influence of pH condition in the preparation of the polyelectrolyte complex capsules on their permeability characteristic for phenylethylene glycol was examined. Partly crosslinked polyelectrolyte complex capsules were prepared by addition of an aqueous poly(acrylic acid) solution into an aqueous poly(ethylenimine) or L-histidine-attached poly(ethylenimine) (ethylenimine unit/L-histidine residue : 5/1, mol/mol) solution and subsequent crosslinking under various pH conditions. Although poly(acrylic acid) and poly(ethylenimine) change their charge density depending on pH in an aqueous solution, the resultant capsules prepared at pHs 7, 6, and 5 show similar permeation properties under neutral and acidic conditions. By contrast, when L-histidine-attached poly(ethylenimine) was used instead of the unmodified polymer as the capsule membrane component, the resultant capsules prepared at pHs 8, 7, and 6 revealed remarkable difference in the permeability under neutral and acidic conditions. Because the ionization of an imidazolyl group, whose pKa is 6, on the L-histidine-attached poly(ethylenimine) is influenced significantly by pH near its pKa, such situation might affect density of networks formed by the ionic bonds in the polyelectrolyte complex membrane and resulted in the permeability difference.