Phototoxicity of coproporphyrin as a novel photodynamic therapy was enhanced by liposomalization.

Abstract

This study attempted the liposomalization of coproporphyrin I (CPI) with hydrophobic properties. Liposomalization of CPI was not successful at any pH when using lactate buffer. In contrast, when using 9% sucrose/10mM phosphate buffer (pH 7.8), CPI liposomes (Lipo-CPI) and polyethyleneglycol (PEG) modified liposomes (PEG-CPI) were prepared with a high entrapment ratio of CPI and small particle size. Plasma CPI concentration at 6h after PEG-CPI injection were 6.5-fold greater than that after the injection of Lipo-CPI. In tumors, the CPI concentration was higher after PEG-CPI injection than after Lipo-CPI or CPI solution. Therefore, PEG-CPI was likely to increase blood circulation and achieve greater accumulation of CPI in the tumor. When loaded into tumor cells, photosensitizers generate singlet oxygen during laser irradiation, resulting in the induction of necrosis in the cells. The order of magnitude of CPI tumor cells uptake was PEG-CPI>Lipo-CPI>CPI solution. Thus, the PEG modification of CPI liposomes improved its tumor cell uptake. Furthermore, it is likely that the order of the ability to produce singlet oxygen was PEG-CPI [symbol: see text] Lipo-CPI>CPI solution. The cytotoxicity of PEG-CPI was significantly greater than the other formulations, suggesting that the cytotoxicity reflected the CPI concentration in tumor cells. In conclusion, PEG-CPI was confirmed to show effective tissue distribution, elevated CPI concentration in the tumor cells, to produce singlet oxygen, and cytotoxicity by PDT.

• Authors: Yasuyuki Sadzuka, Fumiaki Iwasaki, Ikumi Sugiyama, Kentaro Horiuchi, Toru Hirano, Hidechika Ozawa, Naohiro Kanayama, Naoto Oku
• Journal: Toxicology letters (Toxicol Lett) Vol. 182 Issue 1-3 Pg. 110-4 (Nov 10 2008) ISSN: 0378-4274 [Print] Netherlands
• PMID: 18835340 (Publication Type: Journal Article)

Chemical References

• Coproporphyrins
• Drug Carriers
• Liposomes
• Reactive Oxygen Species
• Zinc

Topics

• Animals
• Carcinoma, Ehrlich Tumor (metabolism, therapy)
• Cell Survival (drug effects, radiation effects)
• Coproporphyrins (chemistry, pharmacology, toxicity)
• Dermatitis, Phototoxic
• Drug Carriers
• Electrochemistry
• Light
• Liposomes (chemistry)
• Male
• Mice
• Neoplasm Transplantation
• Particle Size
• Photochemotherapy
• Photons
• Reactive Oxygen Species (chemistry)
• Tissue Distribution
• Zinc (chemistry)