Encapsulation of ganciclovir in albumin nanoparticles enhances the thymidine kinase suicide gene therapy

The therapeutic combination of the herpesvirus thymidine kinase (tk) and ganciclovir has shown great clinical promise as gene therapy for the treatment of hepatocarcinoma. The aim of this study was to evaluate the efficacy of the loading of ganciclovir in albumin nanoparticles to induce hepatoxicity in animals previously treated with adenoviral vectors expressing the tk gene (AdCMVtk). The use of these carriers dramatically increased the drug toxic effects, including high transaminase levels (AST and ALT levels). In addition, the histologic analysis of the liver also revealed a great cellular damage with necrotizing area and perivascular inflammatory reactions. These nanoparticulate carriers offered the additional advantage of increasing the plasmatic half-life of the drug and its tissue distribution, as it was determined by the pharmacokinetic analysis. Thereby, they constitute a very effective system for the prolonged delivery of ganciclovir in vivo, improving the disposition of ganciclovir in the liver.