Liposomal Encapsulation of Ganciclovir Enhances the Efficacy of Herpes Simplex Virus Type 1 Thymidine Kinase Suicide Gene Therapy against Hepatic Tumors in Rats
| Autor: | Carsten Engelmann, Helena Nagy, Yves Panis, Bertrand Diquet, Olivier Soubrane, Monique Fabre, David Klatzmann, Didier Houssin, Jacques Bolard |
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| Rok vydání: | 1999 |
| Předmět: |
Ganciclovir
viruses medicine.medical_treatment Genetic enhancement Lipid Bilayers Herpesvirus 1 Human Pharmacology Biology medicine.disease_cause Antiviral Agents Thymidine Kinase Pharmacokinetics Tumor Cells Cultured Genetics medicine Animals Humans Molecular Biology Phospholipids Drug Carriers Chemotherapy Liver Neoplasms Genetic Therapy Suicide gene Virology Rats Herpes simplex virus Thymidine kinase Colonic Neoplasms Liposomes Toxicity Molecular Medicine medicine.drug |
| Zdroj: | Human Gene Therapy. 10:1545-1551 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/10430349950017879 |
| Popis: | Suicide gene therapy based on ganciclovir (GCV) metabolism by transgene herpes simplex thymidine kinase (HSV-1 TK) has been used to selectively kill proliferating cells in clinical settings such as cancer, vascular restenosis, and immunological disorders. We investigated whether encapsulation of ganciclovir (GCV) into liposomes would improve its efficacy, especially against hepatic tumors. Large unilamellar liposomes containing GCV were prepared by reversed-phase evaporation. Pharmacokinetic studies in rats showed that, compared with free GCV, the intravenous injection of liposome-encapsulated GCV (lip-GCV) led to a faster decrease in GCV plasma concentrations, but higher liver-blood ratios. After treatment of syngeneic HSV-1 TK+ liver metastases in rats, histologically active tumors were found in 95% of the transplanted lesions when physiological saline had been given and in 50% when free GCV had been given at 90.2 microM/kg twice daily. This dose is known to be insufficient for the eradication of HSV-1 TK+ tumors. In contrast, only 5% viable tumors were found in rats receiving lip-GCV at this same concentration. Average tumor volumes were 19 +/- 15, 7 +/- 9, and |
| Databáze: | OpenAIRE |
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