Recent advances in pulmonary drug delivery using large, porous inhaled particles

The abilityto deliver proteins and peptides to the systemic circulation byinhalation has contributed to a rise in the number of inhalationtherapies under investigation. For most of these therapies, aerosolsare designed to comprise small spherical droplets or particles of massdensity near 1 g/cm³ and meangeometric diameter between ~1 and 3 µm, suitable for particlepenetration into the airways or lung periphery. Studies performedprimarily with liquid aerosols have shown that these characteristics ofinhaled aerosols lead to optimal therapeutic effect, both for local andsystemic therapeutic delivery. Inefficient drug delivery can stillarise, owing to excessive particle aggregation in an inhaler,deposition in the mouth and throat, and overly rapid particle removalfrom the lungs by mucocilliary or phagocytic clearance mechanisms. Toaddress these problems, particle surface chemistry and surfaceroughness are traditionally manipulated. Recent data indicate thatmajor improvements in aerosol particle performance may also be achievedby lowering particle mass density and increasing particle size, sincelarge, porous particles display less tendency to agglomerate than(conventional) small and nonporous particles. Also, large, porousparticles inhaled into the lungs can potentially release therapeuticsubstances for long periods of time by escaping phagocytic clearancefrom the lung periphery, thus enabling therapeutic action for periodsranging from hours to many days.