Intratracheal instillation of lipopolymeric vectors and the effect on mice lung physiology

Abstract

Background/Aims: The current study compared the effects of intratracheal administration of different lipopolymeric vectors on lung function and histology in normal mice. Methods: Forty-eight BALB/c mice were randomly divided into 8 groups (6/group). All animals received intratracheal instillation of the following suspensions: polymerized [(A) 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC):1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3- phosphocholine (DC8,9PC):1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), (B) DMPC:DC8,9PC:stearylamine (SA), (C) DMPC:DC8,9PC:myristoylcholine chloride (MCl)]; nonpolymerized [(D) DMPC:DC8,9PC:DOTAP, (E) DMPC:DC8,9PC:SA, (F) DMPC:DC8,9PC:MCl] together with plasmid DNA; vehicle (control), and pDsRed2-N1 plasmid DNA (DNA). At 24 h, the survival rate, lung mechanics (resistive and viscoelastic pressure, static elastance) and morphometry were analyzed. Results: The survival rate was 50% in D, 40% in E and F, and 100% in the CTRL, DNA, A, B and C groups. Animals from groups D, E, and F that died presented diffuse pulmonary hemorrhagic capillaritis. Lung mechanics, the fraction of normal and collapsed alveoli, as well as the number of polymorphonuclear and mononuclear cells in lung tissue were similar in all surviving mice. Conclusion: Intratracheal instillation of polymerized particles is safe compared with nonpolymerized formulations and may be used for future gene/drug therapy.