A comparative study of the bronchodilator effect and duration of action of liposome encapsulated beta-2 adrenergic agonists in the guinea-pig.

The abilities of the adrenergic beta-2 agonists metaproterenol and albuterol in free and liposome encapsulated forms to prevent the bronchoconstrictor response to histamine (10 micrograms/kg i.v.) were compared in anesthetized guinea-pigs. Intratracheal instillation of the unencapsulated adrenergic agonists prevented the histamine bronchoconstriction in a dose dependent fashion. Liposomal metaproterenol was less effective in this regard than the same doses of free drug. In contrast, liposomal albuterol produced an initial bronchodilator effect which was similar to comparable doses of free albuterol but the effect was sustained for a longer duration. These data suggest that intratracheal liposome encapsulated bronchodilators were releashed slowly to the bronchi. This slow release rate reduced the available concentrations of metaproterenol below that required for bronchodilator effects, but the more potent albuterol achieved an active concentration and showed a more sustained duration of action. Further, studies showed that liposome encapsulated material could be aerosolized using a standard air blast nebulizer without significant difference (compared to free drug) in the mass of drug delivered or alteration in the percentage of the drug encapsulated within the liposomes.