The phototoxicity of photofrin was enhanced by PEGylated liposome in vitro

Sadzuka, Yasuyuki; Tokutomi, Koji; Iwasaki, Fumiaki; Sugiyama, Ikumi; Hirano, Toru; Konno, Hiroyuki; Oku, Naoto; Sonobe, Takashi

doi:10.1016/j.canlet.2005.10.024

« Previous Next »Cancer Letters
Volume 241, Issue 1 , Pages 42-48, 8 September 2006

The phototoxicity of photofrin was enhanced by PEGylated liposome in vitro

Yasuyuki Sadzuka
- School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
- Corresponding author. Tel.: +81 54 264 5610; fax: +81 54 264 5615.
Koji Tokutomi
- School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Fumiaki Iwasaki
- School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Ikumi Sugiyama
- School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Toru Hirano
- Photon Medical Research Center, Hamamatsu University School of Medicine 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
Hiroyuki Konno
- Second Department of Surgery II, Hamamatsu University School of Medicine 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
Naoto Oku
- School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Takashi Sonobe
- School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Received 20 January 2005; received in revised form 8 September 2005; accepted 6 October 2005.

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.

Keywords: Liposome, Photodynamic therapy (PDT), Photofrin, Singlet oxygen

Abbreviations: PDT, photodynamic therapy, PF-Lip, photofrin liposome, PF-PEG-Lip, polyethyleneglycol modified photofrin liposome, PF-sol, photofrin solution, DMPC, l-α-dimyristoylphosphatidylcholine, DMPG, l-α-dimyristoylphosphatidyl-dl-glycerol, PEG-DMG, 1-monomethoxypolyethyleneglycol-2,3-dimyristoylglycerol, PBS, phosphate-buffered saline, T_c, transition temperature, EDL, excimer dye laser, PMT, photomultiplier tube, EPR, enhanced permeability and retention