Distribution of free and liposomal doxorubicin after isolated lung perfusion in a sarcoma model.

Détails

ID Serval
serval:BIB_C03EDB2C0612
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Distribution of free and liposomal doxorubicin after isolated lung perfusion in a sarcoma model.
Périodique
Annals of Thoracic Surgery
Auteur(s)
Yan H., Cheng C., Haouala A., Krueger T., Ballini J.P., Peters S., Decosterd L.A., Letovanec I., Ris H.B., Andrejevic-Blant S.
ISSN
1552-6259[electronic]
Statut éditorial
Publié
Date de publication
2008
Volume
85
Numéro
4
Pages
1225-1232
Langue
anglais
Résumé
BACKGROUND: Isolated lung perfusion (ILP) with free and a novel liposomal-encapsulated doxorubicin (Liporubicin, CT Sciences SA, Lausanne, Switzerland) was compared with respect to drug uptake and distribution in rat lungs bearing a sarcomatous tumor. METHODS: A single sarcomatous tumor was generated in the left lung of 39 Fischer rats, followed 10 days later by left-sided ILP (n = 36) with free and equimolar-dosed liposomal doxorubicin at doses of 100 microg (n = 9) and 400 microg (n = 9) for each doxorubicin formulation. In each perfused lung, the drug concentration and distribution were assessed in the tumor and in three areas of normal lung parenchyma by high-performance liquid chromatography (n = 6) and fluorescence microscopy (n = 3). Histologic assessment and immunostaining with von Willebrand factor was performed in 3 animals with untreated tumors. RESULTS: The sarcomatous tumors in controls were well vascularized with fine branching capillaries present throughout the tumors. Isolated lung perfusion resulted in a heterogeneous drug distribution within the perfused lung and a consistently lower drug uptake in tumors than in lung parenchyma for both doxorubicin formulations and both drug doses applied. Isolated lung perfusion with free doxorubicin resulted in a significantly higher drug uptake than Liporubicin in both the tumor and lung tissue for both drug doses applied (p < 0.01). However, the tumor/normal tissue drug ratio was lower for free than for liposomal doxorubicin at a drug dose of 100 microg (0.27 +/- 0.1 vs 0.53 +/- 0.5; p = 0.225) and similar for both doxorubicin formulations at a drug dose of 400 microg (0.67 +/- 0.2 vs 0.54 +/- 0.2; p = 0.335). Both doxorubicin formulations resulted in fluorescence signaling emerging from all tissue compartments of normal lung parenchyma but only in weak and sporadic signaling from the tumors confined to the tumor periphery and vessels situated within the tumor for both drug doses assessed. CONCLUSIONS: Isolated lung perfusion with free and liposomal doxorubicin resulted in a heterogeneous drug distribution within the perfused lung and in a lower drug uptake in tumors than in lung tissue for both doxorubicin formulations and drug doses applied.
Mots-clé
Animals, Cell Line, Tumor, Chemotherapy, Cancer, Regional Perfusion, Disease Models, Animal, Doxorubicin, Liposomes, Lung Neoplasms, Male, Probability, Random Allocation, Rats, Rats, Inbred F344, Reference Values, Sarcoma, Experimental, Sensitivity and Specificity
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/06/2008 10:17
Dernière modification de la notice
20/08/2019 16:34
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