摘要Background:Inhalation-based combination therapy has gained increasing attention for local treatments.However,a key challenge remains in ensuring the sustained pulmonary release of multiple active ingredients,particularly in traditional Chinese medicine(TCM)formulations.Objective:This study investigates a novel PulmoSphere-based inhalable carrier designed for the sustained pulmonary release of mul-tiple active ingredients,using Shuang-Huang-Lian as a model TCM formulation containing three chemical markers.Materials and methods:The carrier was developed using PulmoSphere technology,incorporating phospholipid complexes of the chemical markers and hyaluronic acid(HA)into spray-dried microparticles.The aerodynamic properties,release characteristics,pulmo-nary distribution,and anti-inflammatory efficacy of different formulations were evaluated in vitro and in mice.Results:The microparticles retained the excellent aerodynamic properties of conventional PulmoSphere particles,with a mass median aerodynamic diameter of approximately 3.1 pm and a fine particle fraction of approximately 55％.Compared to free Shuang-Huang-Lian or phospholipid complex-loaded PulmoSphere particles,the HA-containing particles prolonged the retention of chemical markers in the lung epithelial lining fluid,demonstrating sustained release in vivo.Additionally,the HA-containing formulation enhanced the exposure of the three chemical markers to immune cells and lung tissues,leading to improved and prolonged anti-inflammatory effects,even at de-creased doses.Conclusion:This novel inhalable particle system represents a promising approach for sustained pulmonary co-delivery of multiple ac-tive ingredients,offering enhanced and extended local therapeutic efficacy.