Preparation of budesonide-loaded porous PLGA microparticles and their therapeutic efficacy in a murine asthma model.

Inhaling corticosteroids, such as budesonide (BD), is the most common treatment for asthma. However, frequent steroid administration is associated with many side effects. We hypothesized that porous microparticles containing BD could provide an effective treatment method for asthma, as the sustained delivery of corticosteroid and a reduced number of doses could be achieved using porous polymeric microparticles. Porous microparticles were prepared from poly(lactic-co-glycolic acid) (PLGA) by a water-in-oil-in-water double emulsion method with ammonium bicarbonate as the porogen. Varying the porogen concentration controlled the morphology, particle size, and pore size of the PLGA microparticles, with particle size and pore size increasing as the porogen concentration increased. The BD loading efficiency in the porous PLGA microparticles was about 60%, and BD was released from the porous microparticles in a sustained manner for 24h in vitro. Lung uptake efficiency of the porous PLGA microparticles in mice was significantly higher than that of non-porous PLGA microparticles. Budesonide-loaded porous PLGA microparticles were delivered to asthmatic mice, and the numbers of inflammatory cells in bronchoalveolar lavage (BAL) fluid and tissue sections were significantly reduced when the drug was administrated every 3days. We also found significantly reduced bronchial hyperresponsiveness of asthmatic mice after treatment with budesonide-loaded porous PLGA microparticles. This approach to controlling the porous structure of polymeric microparticles, as well as the release behavior of drugs from the microparticles, could have useful applications in the pulmonary delivery of many therapeutic drugs.