title: The phototoxicity of photofrin was enhanced by PEGylated liposome in vitro.
abstract: In recent years, photodynamic therapy (PDT) with a photosensitizer and laser has been given attention, especially for the treatment of superficial cancers, such as lung, gastric, bladder and cervical cancer. In this study, in order to enhance the efficacy of PDT, photofrin liposome (PF-Lip) was prepared with dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol and cholesterol. Polyethyleneglycol modified photofrin liposome (PF-PEG-Lip) was prepared by modification of PF-Lip with monomethoxypolyethyleneglycol-2.3-dimyristoylglycerol. PF-Lip and PF-PEG-Lip entrapped with photofrin with 81.0+/-5.9 and 81.2+/-9.2%, respectively. The particle size of each liposome was 114.3+/-5.7nm (PF-Lip) and 118+/-3.5nm (PF-PEG-Lip), respectively. It was suggested that PEGylated liposomes has no effect on the trapping ratio of PF and particle size. Phototoxicity was enhanced by liposomalization, especially PEG-modification. However, PF-PEG-Lip inhibited the uptake of photofrin into tumor cells. The amount of singlet oxygen from photofrin solution (PF-sol) and each liposome was PF-PEG-Lip=PF-Lip>PF-sol. The photofrin release revel of PF-PEG-Lip was lower than that of PF-Lip. In conclusion, the phototoxicity of PF-PEG-Lip was significantly higher than that of PF-sol or PF-Lip. It is expected that formation of a fixed aqueous layer on the liposome membrane by PEGylation physically changed it into the stable state of PF-PEG-Lip.
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. sadzuka@u-shizuoka-ken.ac.jp
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sadzuka
authors.forename: Koji
authors.initials: K
authors.lastname: Tokutomi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Iwasaki
authors.forename: Ikumi
authors.initials: I
authors.lastname: Sugiyama
authors.forename: Toru
authors.initials: T
authors.lastname: Hirano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
mesh_terms: D045744:Cell Line, Tumor; D017323:Dihematoporphyrin Ether / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D006801:Humans; D008081:Liposomes; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D008081:Liposomes; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D011092:Polyethylene Glycols; D017323:Dihematoporphyrin Ether