Toxicity of cationic liposome-DNA complex in lung isografts

Itaru Nagahiro, Bassem N. Mora, Carlos H.R. Boasquevisque, Ronald K. Scheule, G. Alexander Patterson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Background. Cationic lipids have been successfully employed as vectors for gene transfer in lung grafts, yet those lipid vectors have potential toxicity. Furthermore, the optimal concentration of cationic lipids for gene transfection to lung grafts has not been determined. We evaluated liposome concentration/toxicity relationships in an in vivo rat lung transplantation model. Methods. Left lungs were harvested and infused via the pulmonary artery with chloramphenicol acetyltransferase (CAT)-DNA/lipid 67 (cationic lipid)/dioleoylphosphatidylethanolamine complex (4:1:2 in a final concentration ratio). Donor lungs were allocated into six groups according to lipid 67 concentration: group 1, 0 μM (control); group 2, 10 μM; group 3, 50 μM; group 4, 100 μM; group 5, 250 μM; group 6, 500 μM. Forty-eight hours after orthotopic transplantation, the recipient contralateral right main pulmonary artery and bronchus were ligated. The graft was ventilated with 100% oxygen for 5 min. Arterial blood gas analysis (PaO2, PaCO2), peak airway pressure (PAP), and CAT activity of the grafts were measured. Results. Recipient survival, and PaO2, PAP, and CAT levels correlated with the lipid- DNA complex concentration. The grafts in groups 4-6 were more injured as evidenced by decreased PaO2 and increased PAP levels in comparison to the control group. CAT level was significantly lower in group 2 than in groups 3- 6. Conclusions. The pulmonary toxicity of cationic lipid is dose-dependent. The balance between lung graft function and transgene expression is optimal at a lipid 67 concentration of 50 μM.

Original languageEnglish
Pages (from-to)1802-1805
Number of pages4
JournalTransplantation
Volume69
Issue number9
DOIs
StatePublished - May 15 2000

Fingerprint

Dive into the research topics of 'Toxicity of cationic liposome-DNA complex in lung isografts'. Together they form a unique fingerprint.

Cite this