The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate.
The potential of using poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG-DSPE) polymer to prepare BDP-loaded micelles with high entrapment efficiency and mass median aerodynamic diameter of less than 5 microm demonstrating sustained release properties was evaluated. The result showed that lyophilized BDP-loaded polymeric micelles with entrapment efficiency of more than 96% could be achieved. Entrapment efficiency was affected by both the drug to polymer molar ratio and the amount of drug used. Investigation using FTIR and DSC confirmed that there was no chemical or physical interaction and the drug was molecularly dispersed within the micelles. TEM images showed that the drug-loaded polymeric micelles were spherical in shape with multivesicular morphology. Further analysis by photon correlation spectroscopy indicated that the particle size of the BDP-loaded micelles was about 22 nm in size. In vitro drug release showed a promising sustained release profile over six days following the Higuchi model. The mass median aerodynamic diameter and fine particle fraction were suitable for pulmonary delivery. Moreover, the small amount of deposited drug in the induction port (throat deposition) suggested possible reduction in incidence of oropharyngeal candidiasis, a side effect normally associated with inhaled corticosteroids therapy. The high encapsulation efficiency, comparable inhalation properties, sustained release behavior together with biocompatibility nature of the polymer support the potential of BDP-loaded polymeric micelles as a versatile delivery system to be used in the treatment of asthma and chronic obstructive pulmonary disease.