@misc{oai:repo.qst.go.jp:00071420,
 author = {國領, 大介 and Mi, Peng and Kurita, Tomoka and Yatabe, Teruyuki and Cabral, Horacio and Shibata, Sayaka and Saga, Tsuneo and Aoki, Ichio and Kataoka, Kazunori and et.al and 國領 大介 and 柴田 さやか and 佐賀 恒夫 and 青木 伊知男},
 month = {Feb},
 note = {Introduction: Although intracerebral administration is a promising means to deliver therapeutic drugs beyond the blood-brain barrier to treat brain tumors, it requires safe and sustained release of the drug. We have developed and evaluated a strategy to combine Gd-containing micelles (Gd-micelles) and regularly-structured biodegradable gels (Tetra-PEG gel) to control drug release, to deliver the drug to the tumor with minimal leakage under MRI monitoring.
Method: Tetra-PEG gel was produced by mixing PBS with two polymer materials: tetra-amine-terminated PEG and tetra-NHS (N-hydroxysuccinimide)-glutarate-teminated PEG. Gd-micelles were conjugated with Gd-DOTA and proteasome-inhibitor, and were mixed with Tetra-PEG gel during gel production. To evaluate the in vitro release rate of the Gd-micelles from the gel and the in vivo gel injection using U87MG orthotropic model rats, MRI experiments were performed on preclinical 7.0 Tesla MRI systems. For in vivo experiments, we developed a dual lumen catheter having a single outlet that allows the two polymer solutions to mix inside the tip of the tube. 
Result: The signals from the in vitro gel containing Gd-micelles were gradually decreased for over 42 hours after gel preparation. In the in vivo experiment, the MR signal from the Gd-micelles was locally detected near the injected area with minimal leakage, and was maintained for several days after injection. These indicate that the Gd-micelles were slowly and continuously released from the gel for several days.
Conclusion: The proposed strategy allows slow and controlled release of the drug under MRI monitoring and has the potential to provide effective brain tumor treatment., First合同国際シンポジウム},
 title = {Development of intracerebral drug delivery treatment using a biodegradable gel for slow-release of gadolinium-labeled nano-micelles},
 year = {2014}
}