Liposomes promote pulmonary glucocorticoid delivery

The beneficial effects of glucocorticoids in treating pulmonary inflammatory disorders are complicated by systemic adverse effects. Thus, a possible reduction in dosage and dosing frequency would be advantageous, particularly for patients requiring high doses of the drug. We believe that this can be achieved by developing formulations that increase the retention of glucocorticoids in the lung and a liposome-based drug delivery system may be useful. In the present study, we examined the pulmonary delivery of a liposomal glucocorticoid formulation. Male adult rats were intratracheally instilled with free [3H]dexamethasone (DEX) or [14C]liposome-entrapped [3H]dexamethasone (L-DEX) (800 microg DEX kg body weight) and animals were killed at different times within a 72-h treatment period. Pulmonary retention of [3H]DEX in animals instilled with free DEX was found to be approximately 1.5% of the administered dose 4 h post-instillation, with no radioactivity detectable 24 h post-instillation. Liposome encapsulation of the drug altered the pulmonary retention of DEX with about 34% and 8% of radioactivity remaining in the lung at 4 and 24h post-instillation, respectively. The intratracheal instillation of free DEX or L-DEX reduced the number of leukocytes in peripheral blood to a similar extent (50% of control values) at 4h. However, unlike free-DEX-treated animals whose leukocyte counts returned to control levels by 24h, the circulating leukocyte counts of L-DEX-treated animals remained depressed in the same period. Furthermore, DEX-induced changes in ACTH levels were less evident in animals treated with the liposomal formulation than those treated with free DEX. Our data suggest that the administration of liposome-entrapped DEX has the distinct advantage of enhancing the anti-inflammatory activity of the drug and therefore, possibly reducing its need for frequent administration.