Process Simulation Analysis And Device Optimization Design For Respiratory Tract Delivery Of Inhaled Preparations For Pulmonary Fibrosis

Pulmonary fibrosis(PF)is a chronic and progressive interstitial lung disease with a high mortality rate.Late-stage patients suffer from severe respiratory failure and die painfully.Traditional oral medication for PF can cause side effects such as liver damage.In contrast,inhaled microsphere formulations can directly target the affected area,avoiding first-pass metabolism and greatly reducing damage to the liver and digestive tract.This brings new hope for the treatment of PF.The therapeutic effect of microspheres is related to their size;microspheres that are too small are more likely to be phagocytosed by macrophages in the lungs and lose their therapeutic effect.In addition,clinical symptoms of PF may make it difficult for inhaled agents to enter the respiratory tract.Therefore,this study used numerical simulations and animal experiments to investigate the delivery and deposition process of inhaled microspheres in the respiratory tract,and simulated the deposition distribution of microspheres in an aerosol chamber before entering the respiratory tract.In order to investigate the delivery and deposition process of inhaled microspheres in the respiratory tract,three-dimensional airway models of both human and mouse with pulmonary fibrosis were established,and numerical simulations were conducted using computational fluid dynamics(CFD)method.The delivery and deposition process of porous and non-porous microsphere particles with different sizes and densities were calculated in different degrees of fibrotic airways.The simulation results showed that the pathological state of pulmonary fibrosis was not conducive to the deposition of inhaled microspheres in the bronchi,because fibrosis increased tidal volume and bronchial expansion.Therefore,microspheres were more likely to deposit in the extrathoracic airway region.In addition,the size and density of microspheres had an impact on their deposition.Larger microspheres were more likely to deposit in the extrathoracic airway region due to the stronger inertial impact they received.Among microspheres of the same size,porous microspheres had lower mass and weaker inertial impact,and thus were more likely to cross the extrathoracic airway and deposit in the tracheobronchial region.Based on the numerical simulation results,animal experiments were designed and conducted to study the impact of the pathological state of pulmonary fibrosis and the physical properties(particle size and density)of the microspheres on their deposition in the mouse respiratory tract,and to validate the accuracy of the numerical simulation results.After inhaling microsphere formulations loaded with fluorescent dyes,the fluorescence intensity in the mice was detected and quantified to determine the deposition of microspheres in the respiratory tract.The experimental results showed that the fluorescence intensity in the lungs of pulmonary fibrosis mice was lower than that of healthy mice,indicating that the deposition of microspheres in the lungs of pulmonary fibrosis mice was reduced.Furthermore,the experimental results were consistent with the numerical simulation results.A three-dimensional model mouse nebulization box established used simulate study Microspheres transport distribution outside body nebulization box develop design suitable mouse nebulization experiment distributed nozzle By choosing appropriate distributed nozzle structure enhance uniformity Microspheres distribution nebulization box reduce its wall Deposition Nebulizer jet flow rate has great influence flow field inside nebulization box particle motion trajectory Increasing jet flow rate makes particles follow flow field movement reduce wall Deposition Distributed nozzle improve Microspheres distribution Deposition situation Choosing appropriate jet mode nozzle structure improve uniformity Microspheres distribution reduce waste.This project studies transport distribution situation inside outside respiratory tract by combining simulation animal experiments based on Simulation results design conduct animal Inhalation experiments verify accuracy Simulation Results This project provides theoretical basis support development new Inhalation Microspheres delivery technology materials achieve different individual differences personalized medication achieve precise treatment purpose.