Ikumi Sugiyama*, Hiroki Oikawa, Tomoyuki Masuda and Yasuyuki Sadzuka Pages 668 - 675 ( 8 )
Background: We have previously reported the synthesis of a novel polyethyleneglycol (PEG) lipid, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG (DDA-PEG). This study aimed to clarify the anti-metastatic effect and localization of DDA-PEG-modified liposomes on a murine hepatic metastasis model.Methods: M5076 ovarian sarcoma cells were inoculated for hepatic metastasis model mice. The accumulation of liposomes in the tumor and metastatic sites was detected by fluorescent imaging device. In metastasis study, doxorubicin (DOX) loaded DDA-PEG-modified liposome (DDA-LDOX) was injected. Alexa Fluor 790 NHS Ester loaded DDA-PEG-modified liposomes were used to detect fluorescence intensity at metastatic sites when visualized topically using a fluorescence imaging device. Results: DDA-PEG-modified liposomes accumulated at the sites of hepatic metastasis but not in the normal hepatocytes. Furthermore, the DDA-LDOX inhibited metastasis in this model. The survival time of M5076 ovarian sarcoma bearing mice in DDA-LDOX group was longer than those in control, DOX solution and the other PEG-modified liposomal DOX groups, and the survival ratio in DDALDOX group remained 66.7% until 60 days after treatment. Conclusion: It is expected that the DDA-PEG-modified liposomes will extensively contribute in clinical practice as a superior drug carrier because this liposomes proved to be effective against metastasis.
Fluoresent imaging device, hepatic metastasis, liposome, passive targeting, polyethyleneglycol, tumor affinity.
School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028- 3694, School of Medicine, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, School of Medicine, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694