Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low wate...Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler(LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.展开更多
The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmona...The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmonary drug delivery with references to fluidization research, in particular, studies on Geldart group C powders. Dry powder inhaler device-formulation combination has been shown to be an effective method for delivering drugs to the lung for treatment of asthma, chronic obstructive pulmonary disease and cystic fibrosis. Even with advanced designs, however, delivery efficiency is still poor mainly due to powder dispersion problems which cause poor lung deposition and high dose variability. Drug particles used in current inhalers must be 1–5 μm in diameter for effective deposition in small-diameter airways and alveoli. These powders are very cohesive, have poor flowability, and are difficult to disperse into aerosol due to cohesion arising from van der Waals attraction. These problems are well known in fluidization research, much of which is highly relevant to pulmonary drug delivery.展开更多
Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which...Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance.The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.展开更多
文摘Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler(LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
文摘The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmonary drug delivery with references to fluidization research, in particular, studies on Geldart group C powders. Dry powder inhaler device-formulation combination has been shown to be an effective method for delivering drugs to the lung for treatment of asthma, chronic obstructive pulmonary disease and cystic fibrosis. Even with advanced designs, however, delivery efficiency is still poor mainly due to powder dispersion problems which cause poor lung deposition and high dose variability. Drug particles used in current inhalers must be 1–5 μm in diameter for effective deposition in small-diameter airways and alveoli. These powders are very cohesive, have poor flowability, and are difficult to disperse into aerosol due to cohesion arising from van der Waals attraction. These problems are well known in fluidization research, much of which is highly relevant to pulmonary drug delivery.
基金supported by Pearl River S&T Nova Program of Guangzhou(2014J2200082)
文摘Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance.The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.
