Artikel
Controlled release of mitoxantrone from Ethylene-vinyl acetate copolymer for intracerebral drug delivery
Kontrollierte Freisetzung von Mitoxantron aus Etylen-vinyl-Acetat Bioploymeren für intrazerebrale Medikamentenapplikation
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
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Objective
Mitoxantrone has demonstrated a broad anti-tumoural spectrum in a number of clinical trials as single agent and in combination chemotherapy. However, systemic administration does not reach therapeutical concentration in the brain. In this study we coupled an ethylene-vinyl-acetate copolymer with mitoxantrone to test in vitro and in vivo effects.
Methods
In vitro mitoxantrone was released from the polymeric matrix in a controlled, tapering fashion at a decreasing rate for 30 days. For in vivo studies, rats had mitoxantrone polymers implanted in the brain (i.c.), intraperitoneally (i.p.) or received mitoxantrone injections i.p.. Blood plasma levels of mitoxantrone and leucocyte count were obtained at different time points. Rats were sacrificed at the appearance of irreversible systemic and neurological deterioration and autopsy was performed.
Results
All the rats that were treated with intraperitoneal mitoxantrone injections showed progressive deterioration and died within 8 days after implant. At autopsy, no pathological changes were detected in the extracerebral organs of all animals treated with EVAc implants of mitoxantrone.
Conclusions
The intracerebral implantation of the compound can achieve high levels of mitoxantrone in the brain and reduce systemic toxicity. Controlled intracerebral biopolymer-mediated delivery of mitoxantrone may be of value in the treatment of brain tumors.