Cationic liposome-DNA complexes are being evaluated as potential gene
therapy agents for the lung. Cations have strong effects on the biophy
sical functions of lung surfactant. rant. Therefore, we assessed wheth
er cationic liposomes [composed of N-(1-(2,3-dioleyloxy) propyl)-N,N,N
-trimethyl-ammonium chloride and dioleylphosphatidylethanolamine] with
or without DNA affect behavior of four types of surfactant in vitro.
Experiments were carried out using a modified Wilhelmy surface balance
. The ability of surfactants that contain protein and anionic lipids t
o lower surface tension was inhibited in the presence of cationic lipo
somes. Inactivation was less when DNA was preincubated with cationic l
iposomes. Surfactant that contained neither protein nor anionic lipids
was not inactivated. Mechanical properties of the lung were studied t
o assess in vivo surfactant function after intratracheal instillation
of a cationic liposome-DNA complex into adult rats. Pressure-volume de
flation curves were shifted by 18% compared with those from normal (un
treated) animals, but this effect was transient and not different from
that observed in animals who received a similar volume of saline. The
se findings indicate that cationic liposomes alone may have deleteriou
s effects on behavior of some surfactants possibly by disrupting charg
e interactions between negatively charged phospholipids and surfactant
proteins. When DNA is added to liposomes before exposure to surfactan
ts, the adverse charge interactions may be obviated by charge neutrali
zation of liposomes by DNA.