Article
Experimental gliossarcoma genetic therapy: Use of a silicon formulation with ganciclovir
Experimentelle Gliossarkoma-Therapie: Gebrauch von einer Silikon-Formulierung mit Ganciclovir
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Published: | April 23, 2004 |
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Outline
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Objective
- Evaluate the efficiency of a silocone formulation for intratumoral release of ganciclovir in experimental gliossarcoma treated with genetic therapy (enzyme, pro-drug) - Study the biodisponibility and safety of ganciclovir realesed by this silicone formulation, compared with convetional routes of administration
Methods
- Cellular culture and virus production - Preparation of a silicone formulation with ganciclovir (GCV) - Studies of GCV liberation "in vitro" - Essays of citotoxicity of GCV "in vitro" - Implantation "in vivo" of tumoral cells and viral inoculation - Intracerebral distribution of GCV measured by Fase Revertion High Resolution Liquid Cromatography - Statistical evaluation
Results
Sustained release of low dose gangiclovir from a silicone formulation prolonged the survival of rats with gliossarcoma under Herpes Simplex virus thymidine kinase suicide gene therapy.
Conclusions
- Sustained release of low dose gangiclovir from a silicone formulation prolonged significantly the survival of "Fischer 344" rats with gliossarcoma 9L, treated with T1 virus, expressing the thymidine kinase Herpes Simplex 1 enzyme, when compared with the intraperitoneal inoculation of ganciclovir. - The histopathological analysis of the cerebral tissue around the cavity occuped by the silicone formulation suggests that it causes little inflamatory reaction and no imunological reaction. - The biodisponibility study of the ganciclovir released by the silicone formulation shows that the intratumoral concentration of the drug was effective for the studied modell, whereas the blood concentration was indetectable.