LARGE POROUS PARTICLES EMITTED FROM AN INHALER

摘要

Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 νm and 30 νm, which together yield an aerodynamic diameter of the particles of between approximately one and five microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may comprise a therapeutic, prophylactic or diagnostic agent and a material selected from the group consisting of surfactant and a molecule having a charge opposite to the charge of the agent and forming a complex thereto. The particles have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 νm and 30 νm. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles are administered to the respiratory tract to permit systemic or local delivery of a wide variety of therapeutic agents. Aggregation of particles before or during administration to the respiratory tract results in particles having an aerodynamic diameter larger than that of the fully dispersed particles. Aerodynamic diameters between three and five microns are advantageous for delivery to the central airways.