Intratracheal Instillation of Lipopolymeric Vectors and the Effect on Mice Lung Physiology

DEBORA G. XISTO; CARLOS FACUNDO TEMPRANA; SABRINA V. MARTINI; ADRIANA L. SILVA; SORAIA G. ABREU; JOHNATAS D. SILVA; JULIA CROSSETI; PATRICIA R. M. ROCCO; SILVIA DEL VALLE ALONSO; MARCELO M. MORALES

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY : INTERNATIONAL JOURNAL OF EXPERIMENTAL CELLULAR PHYSIOLOGY, BIOCHEMISTRY, AND PHARMACOLOGY.

KARGER

Lugar: Basel; Año: 2012 vol. 29 p. 791 - 798

1015-8987

Background/Aims: The current study comparedthe effects of intratracheal administration ofdifferent lipopolymeric vectors on lung function andhistology in normal mice. Methods: Forty-eightBALB/c mice were randomly divided into 8 groups(6/group). All animals received intratrachealinstillation 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), andpDsRed2-N1 plasmid DNA (DNA). At 24 h, the survivalrate, lung mechanics (resistive and viscoelasticpressure, static elastance) and morphometry wereanalyzed. Results: The survival rate was 50% in D, 40% in E and F, and 100% in the CTRL, DNA, A, Band C groups. Animals from groups D, E, and F thatdied presented diffuse pulmonary hemorrhagiccapillaritis. Lung mechanics, the fraction of normaland collapsed alveoli, as well as the number ofpolymorphonuclear and mononuclear cells in lungtissue were similar in all surviving mice. Conclusion:Intratracheal instillation of polymerized particles is safecompared with nonpolymerized formulations and maybe used for future gene/drug therapy.