Ayumi Kashiwada

Internal stimuli-responsive controlled release from liposomal vesicles is an innovative approach for site-specific delivery of therapeutic drugs. In this study, to enhance the endosomal pH control of drug release from liposomes, a series of histidine-modified pH-sensitive Cn-His (n = 8, 12, 18) agents were designed and utilized as triggers for liposomal content release. The pH-dependent properties of Cn-His-incorporated liposomes were characterized using dynamic light scattering, ζ-potential, and fluorescence spectroscopy. The liposomes maintained a relatively uniform size across all pH conditions. However, the ζ-potential exhibited positive values at endosomal acidic pH levels and neutral or negative values at physiological pH levels. Furthermore, acidic pH-dependent release of both polar content (carboxyfluorescein) and nonpolar content (Nile red) was observed from the Cn-His-incorporated liposomes. Notably, with C12-His as the pH sensitizer, the pH dependence of liposomal content release was significantly evident. This work establishes endosomal pH-controllable liposome platforms, laying the groundwork for developing clinically applicable triggered release formulations.

Liposomes are well-investigated drug or gene delivery vehicles for chemotherapy, used by taking advantage of their biocompatibility and biodegradability. A central question on the construction of intracellular liposomal delivery systems is to entrap the liposomes of interest in the highly acidic and proteolytic endosomal environment. In the other words, it is essential that the liposomes release a therapeutic drug into the cytosol before they are degraded in the endosome. As a strategy to enhance the endosome escape, the self-lytic liposomes with acidic pH-selective membrane active polypeptide are considered highly effective. Here, an acidic pH-selective membrane-lytic polypeptide (LPE) and its retro isomer (rLPE) were designed, and then their membrane-lytic activities against EggPC liposomes were determined. It was noticed that the rLPE polypeptide showed an increase in activity compared with the LPE polypeptide. Furthermore, the rLPE polypeptide was conjugated to liposomes via a flexible Gly-Gly-Gly-Gly linker to facilitate the pH-selective content release. The rLPE anchoring liposomes exhibited distinctly different contents release behavior at physiological and endosomal pHs, namely typical contents release from liposomes was positively observed at acidic pH range. The overarching goal of this paper is to develop efficient pH-selective therapeutic delivery systems by using our findings.

Removal of linear and branched alkylphenols with different alkyl chain lengths or different branchings (normal, secondary, and tertiary), some of which are suspected as endocrine disrupting chemicals, from an aqueous medium were investigated through quinone oxidation by polyphenol oxidase (PPO) and subsequent quinone adsorption on chitosan beads or powders at pH 7.0 and 40 °C. PPO-catalyzed quinone oxidation increased with an increase in alkyl chain length of the alkylphenols used. Although a higher PPO dose was required for quinone oxidation of branched alkylphenols, they were completely or mostly removed by quinone adsorption on chitosan beads or powders. The apparent activity of PPO increased by a decrease in quinone concentration. On the other hand, in the homogeneous systems with solutions of chitosan and PPO at pH 6.0, longer reaction times were required to generate insoluble aggregates, and a small amount of quinone derivatives were left in the solution even under optimum conditions. These results support that the two-step reaction, that is, PPO-catalyzed quinone oxidation and subsequent quinone adsorption on chitosan beads or powders, in the heterogeneous system is a good procedure for removing linear and branched alkylphenols from aqueous medium.

The bicomponent blends in isobutenyl compounds showed 2D structural modulation due to odd–even effect as well as blend ratio-dependent 2D structural change.

Effective acidic pH-selective liposomal membrane lysis was achieved by using a novel designed peptide.

In this study, enzymatic removal of bisphenol A (BPA) from the aqueous medium was investigated through the generation of water-insoluble oligomers, and this procedure was applied to removal of bisphenol derivatives. The experimental parameters, such as the temperature, pH value, enzyme concentration, and concentration and molecular weight of polyethylene glycol (PEG), were determined for the laccase-catalyzed treatment of BPA. The optimum conditions were determined to be pH 7.0 and 40°C in the absence of PEG. Water-insoluble oligomers generated under these conditions were readily removed by filtration or centrifugation. The optimum pH value was decreased to 5.0 in the presence of PEG and the laccase dose was reduced to one-fiftieth of that in the absence of PEG. This indicates that the addition of PEG protects the enzymatic activity and prevents capture of laccase molecules in the oligomers. The oligomers generated in the presence of PEG were removed from the aqueous medium by filtration with a membrane filter or by centrifugation. The oligomers were completely filtrated out with a filter paper by decreasing the pH value to 3.0. In addition, several bisphenol derivatives were also treated and subsequently removed by adjusting the laccase dose in the presence of PEG using the above procedure.

In this study, the combined use of a biopolymer chitosan and an oxidoreductase polyphenol oxidase (PPO) was systematically investigated for the removal of bisphenol derivatives from aqueous medium. The process parameters, such as the pH value, temperature, and PPO concentration, were estimated to conduct the enzymatic quinone oxidation of bisphenol derivatives by as little enzyme as possible. Bisphenol derivatives effectively underwent PPO-catalysed quinone oxidation without H₂O₂ unlike other oxidoreductases, such as peroxidase and tyrosinase, and the optimum conditions were determined to be pH 7.0 and 40°C for bisphenol B, bisphenol E, bisphenol O, and bisphenol Z; pH 7.0 and 30°C for bisphenol C and bisphenol F; and pH 8.0 and 40°C for bisphenol T. They were completely removed through adsorption of enzymatically generated quinone derivatives on chitosan beads or chitosan powders. Quinone adsorption on chitosan beads or chitosan powders in the heterogeneous system was found to be a more effective procedure than generation of aggregates in the homogeneous system with chitosan solution. The removal time was shortened by increasing the amount of chitosan beads or decreasing the size of the chitosan powders.

The 2D structures of bicomponent blends in isobutenyl compounds were observed by using scanning tunneling microscopy at the solid/liquid interface. Amplification of the alkyl chain effect was found on the 2D structures.

In this study, the combined use of an amino group-containing polymer chitosan and an oxidoreductase polyphenol oxidase (PPO) was applied to the removal of naphthols and dihydroxynaphthalenes (DHNs) from aqueous solutions. The process parameters, such as the pH value, temperature and enzyme dose, were discussed for PPO-catalysed oxidation of 1-naphthol. The optimum conditions of enzymatic oxidation of 1-naphthol were determined to be pH 8.0 and 40 °C. Under the optimum conditions, PPO-catalysed oxidation of 1-naphthol increased with an increase in the enzyme dose. Quinone derivatives enzymatically generated were chemisorbed on chitosan beads and the initial velocity of PPO-catalysed oxidation increased with an increase in the amount of added chitosan beads. A specific initial velocity of 0.0675 μmol/U·min was obtained in the PPO concentration range below 200 U/cm³ and 1-naphthol was completely removed within 24 h by quinone adsorption on chitosan beads (0.20 cm³/cm³) at a PPO concentration of 100 U/cm³. The removal time was shortened by increasing the enzyme dose or the amount of added chitosan beads. 2-Naphthol was also completely removed at an initial concentration of 0.05 mM or less by prolonging the reaction time, since PPO-catalysed oxidation of 2-naphthol was much slower than that of 1-naphthol. In addition, this procedure was also applied to the removal of DHNs. These results revealed that the procedure constructed in this study was an effective technique to remove naphthols and DHNs from the aqueous medium.