Establishment of novel strategy in cancer treatments based on modulation of microenvironment of tumor tissues

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590194
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Okayama University
• Principal Investigator: OGAWARA Ken-ichi 岡山大学, 医歯(薬)学総合研究科, 准教授 (30291470)
• Co-Investigator(Kenkyū-buntansha): HIGAKI Kazataka 岡山大学, 大学院医歯薬学総合研究科, 教授 (60284080)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: がん治療 / 抗がん剤 / 血管正常化 / リポソーム / エマルション / 抗腫瘍効果 / 局所動態

Outline of Final Research Achievements

The effect of pre-treatment with SU5416, a selective VEGF receptor-2 inhibitor, on tumor disposition and in-vivo anti-tumor activity of polyethylene glycol (PEG)-modified liposomal paclitaxel (PL-PTX) was evaluated. To improve the solubility of SU5416, the inhibitor was formulated in PEGylated O/W emulsion (PE-SU5416). Pre-treatment with PE-SU5416 significantly enhanced the in-vivo anti-tumor effect of PL-PTX. The pretreatment with PE-SU5416 improved the tumor vessel functions, including oxygen supply. Furthermore, the pre-treatment with PE-SU5416 increased the distribution of PEG liposomes and included PTX in the core region of the tumor. These results suggest that the functional normalization of the tumor vasculature by the pre-treatment with PE-SU5416 enabled liposomes to reach the deeper regions within tumor tissues, leading to more potent anti-tumor activity of PL-PTX.

Free Research Field

DDS, 製剤学, 薬剤学