Pulmonary Uptake of Liposome-associated α-Tocopherol Following Intratracheal Instillation in Rats

Abstract

Abstract This study examined the uptake and subcellular distribution of α-tocopherol in the lung following intratracheal instillation of liposome-associated α-tocopherol in rats. The liposomal suspension was composed of dipalmitoylphosphatidylcholine (DPPC) and α-tocopherol (molar ratio 7:3), labelled with [3H]α-tocopherol and [14C]cholesterol. Following intratracheal administration of the liposomal preparation (2 mg α-tocopherol/animal), the recovery of [3H]α-tocopherol in the lung was maximal (87% of initial dose) 1 h after treatment; thereafter, α-tocopherol levels remained relatively high (no less than 73% of initial dose) for the rest of the 72-h experimental period. This treatment effect resulted in a 16-fold increase in pulmonary total α-tocopherol concentration 72 h post-instillation. No radioactivity was detected in the blood, liver, kidney, pancreas, spleen and heart of animals during the 72-h experimental period. [3H]α-Tocopherol was recovered largely from cytosolic (45%) and nuclear (36%) fractions of lung and to a lesser extent, from microsomal (11%) and mitochondrial (9%) fractions. Chromatographic analysis of the subcellular fractions revealed that [3H]α-tocopherol was co-eluted with 14C-labelled liposomal lipids. Our in-vitro study, involving the incubation of Fe3+-ADP (a pro-oxidant) with mitochondrial or microsomal fractions isolated from lung tissues of animals treated with liposome-associated α-tocopherol, provided evidence that α-tocopherol levels present in the membranes of these subcellular fractions were sufficient to protect against oxidant-induced lipid peroxidation. α-Tocopherol in the rat lung can be greatly increased by the intratracheal instillation of α-tocopherol entrapped in DPPC-liposomes, suggesting that this liposomal preparation may be used as an effective prophylactic agent against oxidant-induced lung injury.