Non-phospholipid vesicles for pulmonary glucocorticoid delivery

Abstract

In the formulation of inhaled drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD), considerable attention has been devoted to new aerosol morphologies which can either enhance the local effect and/or increase the penetration through the mucus, secreted in bronchial inflammatory diseases. In diseases characterized by bronchial hypersecretion, lipophilic substances, such as corticosteroids, can be remarkably impeded in reaching their receptors, which are localized within the cytoplasm of bronchial epithelial cells. Vesicles consisting of one or more surfactant bilayers enclosing aqueous spaces, are of particular interest because they offer several advantages with regard to chemical stability, lower cost and availability of materials compared to conventional liposomes. With the purpose of carrying out research leading to an innovative formulation for lung delivery capable of permeating the mucous layer, beclomethasone dipropionate, clinically used for the treatment of asthma and COPD, was entrapped in non-phospholipid vesicles. The composition providing the highest entrapment efficiency was chosen. The vesicles obtained after jet nebulization were characterized by means of freeze-fracture microscopy and dynamic light scattering. The efficiency of this new drug delivery system was evaluated in vitro with simulated mucus by means of diffusion experiments (three compartment cell apparatus), using 0.1% mucin gel-like dispersion as a barrier to drug permeation.