Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts

Michiko Yokosawa, Yukihiko Sonoda, Shin ichiro Sugiyama, Ryuta Saito, Yoji Yamashita, Masamichi Nishihara, Taku Satoh, Toshihiro Kumabe, Masayuki Yokoyama, Teiji Tominaga

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Prognosis for the patients with glioblastoma, the most common malignant brain tumor, remains dismal. A major barrier to progress in treatment of glioblastoma is the relative inaccessibility of tumors to chemotherapeutic agents. Convection-enhanced delivery (CED) is a direct intracranial drug infusion technique to deliver chemotherapeutic agents to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED can provide wider distribution of infused agents compared to simple diffusion. We have reported that CED of a polymeric micelle carrier system could yield a clinically relevant distribution of encapsulated agents in the rat brain. Our aim was to evaluate the efficacy of CED of polymeric micellar Am80, a synthetic agonist with high affinity to nuclear retinoic acid receptor, in a rat model of glioblastoma xenografts. We also used systemic administration of temozolomide, a DNA-alkylating agent, which has been established as the standard of care for newly diagnosed malignant glioma. U87MG human glioma cells were injected into the cerebral hemisphere of nude rats. Rats bearing U87MG xenografts were treated with CED of micellar Am80 (2.4 mg/m2) on day 7 after tumor implantation. Temozolomide (200 mg/m2/day) was intraperitoneally administered daily for 5 days, starting on day 7 after tumor implantation. CED of micellar Am80 provided significantly longer survival than the control. The combination of CED of micellar Am80 and systemic administration of temozolomide provided significantly longer survival than single treatment. In conclusion, temozolomide combined with CED of micellar Am80 may be a promising method for the treatment of malignant gliomas.

Original languageEnglish
Pages (from-to)257-264
Number of pages8
JournalTohoku Journal of Experimental Medicine
Volume221
Issue number4
DOIs
Publication statusPublished - Jul 13 2010

Fingerprint

Bearings (structural)
Convection
temozolomide
Retinoids
Micelles
Glioblastoma
Heterografts
Rats
Tumors
Glioma
Brain
Drug infusion
Central Nervous System Agents
Nude Rats
Neoplasms
Retinoic Acid Receptors
Survival
tamibarotene
Alkylating Agents
Cerebrum

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts. / Yokosawa, Michiko; Sonoda, Yukihiko; Sugiyama, Shin ichiro; Saito, Ryuta; Yamashita, Yoji; Nishihara, Masamichi; Satoh, Taku; Kumabe, Toshihiro; Yokoyama, Masayuki; Tominaga, Teiji.

In: Tohoku Journal of Experimental Medicine, Vol. 221, No. 4, 13.07.2010, p. 257-264.

Research output: Contribution to journalArticle

Yokosawa, Michiko ; Sonoda, Yukihiko ; Sugiyama, Shin ichiro ; Saito, Ryuta ; Yamashita, Yoji ; Nishihara, Masamichi ; Satoh, Taku ; Kumabe, Toshihiro ; Yokoyama, Masayuki ; Tominaga, Teiji. / Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts. In: Tohoku Journal of Experimental Medicine. 2010 ; Vol. 221, No. 4. pp. 257-264.
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