Photochemical control of micellar solubilization of an oily substance was investigated using the photoisomerization of 4-butylazobenzene-4‘-(oxyethyl)trimethylammonium bromide (AZTMA), a cationic surfactant modified with azobenzene. Examination of the effect of ultraviolet and visible light irradiation on the UV/vis absorption spectrum of aqueous AZTMA solution revealed that the surfactant undergoes reversible isomerization between the trans and cis forms. The critical micelle concentrations (cmc) of the two isomers determined electroconductometrically were 2.7 mM for the trans form and 8.2 mM for the cis form, respectively. Ultraviolet irradiation of aqueous trans-AZTMA solution with solubilized ethylbenzene caused photoisomerization of the trans isomer to release a part of the solubilized ethylbenzene. Subsequent visible light irradiation of the aqueous cis-AZTMA solution produced photoisomerization to the trans isomer to resolubilize the released ethylbenzene. Such control by light of micellar solubilization of an oily substance was found to arise from the differences in both the number and solubilizing capacity of micelles between the two isomers.

The effects of poly(ethylene glycol) (PEG) chain length of PEG-lipid on the membrane characteristics of liposomes were investigated by differential scanning calorimetry (DSC), freeze-fracture electron microscopy (FFEM), fluorescence polarization measurement and permeability measurement using carboxyfluorescein (CF). PEG-liposomes were prepared from mixtures of dipalmitoyl phosphatidylcholine (DPPC) and distearoyl phosphatidylethanolamines with covalently attached PEG molecular weights of 1000, 2000, 3000 and 5000 (DSPE-PEG). DSC and FFEM results showed that the addition of DSPE-PEG to DPPC in the preparation of liposomes caused the lateral phase separation both in the gel and liquid-crystalline states. The fluidity in the hydrocarbon region of liposomal bilayer membranes was not significantly changed by the addition of DSPE-PEG, while that in the interfacial region was markedly increased. From these results, it was anticipated that the CF leakage from PEG-liposomes is accelerated compared with DPPC liposomes. However, CF leakage from liposomes containing DSPE-PEG with a 0.060 mol fraction was depressed compared with regular liposomes, and the leakage decreased with increasing PEG chain length. Furthermore, the CF leakage from liposomes containing DSPE-PEG with a 0.145 mol fraction was slightly increased compared with that of liposomes containing DSPE-PEG with a 0.060 mol fraction. It is suggested that the solute permeability from the PEG-liposomes was affected by not only properties of the liposomal bilayer membranes such as phase transition temperature, phase separation and membrane fluidity, but also the PEG chain of the liposomal surface.

Liposomal drug delivery systems (DDS) have been widely researched for use in drug toxicity reduction and/or drug targeting to desired target tissues.1) However, liposomes are rapidly removed from the circulation following their intravenous administration primarily by Kupffer cells in the liver and fixed macrophages in the spleen. Thus, it is important to develop modified liposomes that are able to avoid uptake by the reticuloendothelial system (RES) and extend their circulation half-life in vivo. Many studies have reported that the conjugation of amphipathic polyethylene glycol (PEG) with liposomes (PEG-liposomes) significantly increases the blood circulation liposome half-life compared with those without PEG. [2][3][4][5] In our previous studies, 6,7) we reported on the effect of PEG-lipid PEG chain length on the membrane characteristics of liposomes. The addition of PEG-lipid to liposomes caused lateral phase separation in the gel and liquid-crystalline states, and the fluidity in the interfacial region of liposomal bilayer membranes was markedly increased by the addition of PEG-lipids. In addition, the permeability of liposomal bilayer membranes decreased compared with those without PEG. From these results, we concluded that the solute permeability of PEG-liposomes is affected by not only the properties of the liposomal bilayer membranes such as phase separation and membrane fluidity, but also the PEG chain length of the liposomal surface.In this study, we investigated the effects of PEG-lipid concentration on CF leakage from PEG-liposomes to elucidate the permeation mechanism of PEG-liposomes in more detail. ExperimentalMaterials L-a -Dipalmitoylphosphatidylcholine (DPPC, 99.6% pure) was obtained from NOF Co., Ltd., and Distearoyl-N-monomethoxy poly-(ethylene glycol)-succinyl-phosphatidylethanolamines (DSPE-PEG) were acquired from NOF Co., Ltd. (Tokyo, Japan). The weight-average molecular weights of poly(ethylene glycol) were 1000, 2000, 3000 and 5000. 5-(6)-Carboxyfluorescein (CF, 99% pure) was purchased from Molecular Probes, Inc. (OR, U.S.A.) and was used without further purification. 1,6-Diphenyl-1,3,5-hexatriene (DPH, 98% pure) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH, 95% pure) were purchased from Sigma Chemical Co. (MO, U.S.A.) and were also used without further purification. Dulbecco's Phosphate-buffered saline (PBS) powder composed of NaCl, KCl, Na 2 HPO 4 and KH 2 PO 4 was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). PBS powder was dissolved in water for injection (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan), and an isotonic solution of pH 7.4 was used. All other chemicals were commercial products of reagent grade.Preparation of PEG-Liposomes PEG-liposomes were prepared using DPPC and DSPE-PEG, which were first dissolved in chloroform in a test tube. The solvent was then removed by blowing nitrogen gas into the test tube, and the residual solvent was further dried overnight at room temperature in a desiccator under a vacuum. PBS was added to the ...