The therapeutic efficacy of conjugated linoleic acid - paclitaxel on glioma in the rat.
Considering the effects of conjugated linoleic acid (CLA) on anti-tumor and anti-angiogenic in brain tumor, synergistic anti-tumor activity with taxane as well as potential activity for transporting chemotherapeutic agents across the blood-brain barrier (BBB), the purpose of this study was to synthesize CLA-paclitaxel (CLA-PTX) conjugate which could reach to the brain tissue and target brain tumor. The CLA was covalently linked to PTX. The conjugate was stable in PBS and rat plasma in vitro and had no microtubule assembly activity in solution and slight effect of arresting cell cycle progression at the G(2)-M phase. The in vitro cytotoxicity of conjugate was lower than that of PTX (p < 0.05). The conjugate showed higher cellular uptake efficiency on C6 glioma cells. The entire pharmacokinetic index revealed the significant enhancement of the conjugate pharmacokinetics compared with that in PTX (p < 0.01). The conjugate, unlike PTX, could distribute in brain tissue and retained higher concentrations throughout 360 h. The anti-tumor efficacy in brain tumor-bearing rats after administering conjugate was significantly higher than that after giving Taxol (p < 0.01). In conclusion, this CLA-PTX conjugate showed great potential to become a new prodrug of PTX and the methodology can be applied to other anticancer drugs.
Ke
Xi-Yu
XY
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Zhao
Bo-Jun
BJ
Zhao
Xin
X
Wang
Ying
Y
Huang
Yue
Y
Chen
Xiao-Mei
XM
Zhao
Bing-Xiang
BX
Zhao
Shan-Shan
SS
Zhang
Xuan
X
Zhang
Qiang
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D044243:Linoleic Acids, Conjugated / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D017239:Paclitaxel / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D044243:Linoleic Acids, Conjugated; D014404:Tubulin; D017239:Paclitaxel