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

The Tohoku Journal of Experimental Medicine
Michiko YokosawaTeiji Tominaga

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/m(2)) on day 7 after tumor implantation. Temo...Continue Reading

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Citations

Jan 28, 2012·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Guifa XiStewart Goldman
Jul 24, 2014·CNS Oncology·Toral R Patel
Oct 1, 2011·Drug Development and Industrial Pharmacy·Shadabul HaqueSanjula Baboota
Jan 3, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lindsey CrawfordDavid Putnam
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Oct 9, 2020·Advanced Drug Delivery Reviews·Aroa Duro-CastanoGiuseppe Battaglia

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