Pulmonary uptake of liposome-associated alpha-tocopherol following intratracheal instillation in rats
Suntres, Z.E.; Hepworth, S.R.; Shek, P.N.
Journal of Pharmacy and Pharmacology 45(6): 514-520
1993
ISSN/ISBN: 0022-3573 PMID: 8103098 Document Number: 420096
This study examined the uptake and subcellular distribution of alpha-tocopherol in the lung following intratracheal instillation of liposome-associated alpha-tocopherol in rats. The liposomal suspension was composed of dipalmitoylphosphatidylcholine (DPPC) and alpha-tocopherol (molar ratio 7:3), labelled with (3H) alpha-tocopherol and (14C)cholesterol. Following intratracheal administration of the liposomal preparation (2 mg sbd tocopherol/animal), the recovery of (3H)alpha-tocopherol in the lung was maximal (87% of initial dose) 1 h after treatment; thereafter, alpha-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 alpha-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)alpha-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)alpha-tocopherol was co-eluted with 14C-labelled liposomal lipids. Our in vitro study, involving the incubation of Fe-3+-ADP (a pro-oxidant) with mitochondrial or microsomal fractions isolated from lung tissues of animals treated with liposome-associated alpha-tocopherol provided evidence that alpha-tocopherol levels present in the membranes of these subcellular fractions were sufficient to protect against oxidant induced lipid peroxidation. alpha-tocopherol in the rat lung can be greatly increased by the intratracheal instillation of alpha-tocopherol entrapped in DPPC-liposomes, suggesting that this liposomal preparation may be used as an effective prophylactic agent against oxidant-induced lung injury.