9th Asian Cyclodextrin Conference (9ACC)
タイトル；Efficient Anticancer Drug Delivery for Pancreatic Cancer Utilizing Reversible PEGylated Bromelain.
発表者；古後 徹也 氏
（熊本大学 大学院薬学教育部 製剤設計学分野）
INTRODUCTION: Of various cancers, pancreatic cancer has been known as one of the most difficult-to-treat cancers because of inhibition of the penetration of anticancer drugs into the cancer tissues, resulting from the dense extracellular matrix (ECM). On the other hand, bromelain is known to degrade the ECM in the cancer tissue. However, blood half-life of bromelain is short, leading to its low accumulation in cancer. Recently, we developed the novel reversible polyethylene glycol (PEG) modification technology which is able to improve blood retention of proteins without loss of the activity, and termed it “Self-assembly PEGylation Retaining Activity (SPRA)” technology. Therefore, in this study, we prepared PEGylated bromelain through SPRA technology (SPRA-Br) and evaluated its possibility as anticancer agent delivery system for pancreatic cancer.
METHODS: SPRA-Br was prepared by mixing adamantane-appended bromelain (Ad-Br) and PEGylated -cyclodextrin. In vitro enzyme activity of SPRA-Br and covalently PEGylated bromelain (PEG-Br) was evaluated by measuring gelatin degradation ability. Pancreatic cancer model was prepared by subcutaneously injection of MIA PaCa-2 cells with Matrigel® to BALB/c nu/nu male mice. Then, SPRA-Br was intravenously injected to the mice. After 24 h, doxorubicin (low-molecular weight drugs) or DOXIL® (doxorubicin capsulated in PEGylated liposome) was also intravenously injected once a week to the mice and tumor volume was measured.
RESULTS AND CONCLUSIONS: Gelatin-degrading activity of SPRA-Br was almost retained compared with bromelain alone, whereas that of PEG-Br was completely diminished. Additionally, pre-treatment with SPRA-Br enhanced the antitumor activity of both doxorubicin and DOXIL in pancreatic cancer model mice. These results suggest that, SPRA-Br could be useful as a highly efficient anticancer drug delivery system for pancreatic cancer.