The purpose of this study was to develop
antioxidant liposomes as an
antidote for
mustard gas-induced
lung injury in a guinea pig model. Five
liposomes (LIP-1, LIP-2, LIP-3, LIP-4, and LIP-5) were tested with differing levels of
phospholipid,
cholesterol,
phosphatidic acid,
tocopherol (alpha, gamma, delta),
N-acetylcysteine (NAC), and
glutathione (GSH). A single dose (200 microL) of
liposome was administered intratracheally 5 min or 1 h after exposure to
2-chloroethyl ethyl sulfide (
CEES). The animals were sacrificed either 2 h after exposure (for
lung injury study) or 30 days after exposure (for histology study). The
liposomes offered 9%-76% protection against
lung injury. The maximum protection was with LIP-2 (71.5% protection) and LIP-4 (75.4%) when administered 5 min after
CEES exposure. Delaying the
liposome administration 1 h after
CEES exposure decreased the efficacy. Both
liposomes contained 11 mM
alpha-tocopherol, 11 mM
gamma-tocopherol, and 75 mM NAC. However, LIP-2 contained additionally 5 mM
delta-tocopherol. Overall, LIP-2 and LIP-4 offered significant protection by controlling the recruitment of neutrophils, eosinophils, and the accumulation of septal and perivascular
fibrin and
collagen. However, LIP-2 showed better protection than LIP-4 against the accumulation of red blood cells in the bronchi, alveolar space, arterioles and veins, and
fibrin and
collagen deposition in the alveolar space. The antifibrotic effect of the
liposomes, particularly LIP-2, was further evident by a decreased level of lipid peroxidation and
hydroxyproline in the lung. Thus,
antioxidant liposomes containing both NAC and
vitamin E are an effective
antidote against
CEES-induced
lung injury.