BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical e...BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.展开更多
The purpose of this study was to investigate the spray dried lactose as carrier for dry powder inhalation(DPI).The lactose particles were prepared by spray drying,then the particle size,shape and crystal form were cha...The purpose of this study was to investigate the spray dried lactose as carrier for dry powder inhalation(DPI).The lactose particles were prepared by spray drying,then the particle size,shape and crystal form were characterized by laser diffraction,scanning electron microscopy(SEM),X-ray diffraction(XRD)and differential scanning calorimetry(DSC).The spray dried lactose particles were spherical and amorphous,but would transfer to crystal form when storage humidity was above 32%.Thus,the humidity of the storage environment should be controlled below 30%strictly in order to maintain the amorphous nature of spray dried lactose which is a great benefit to DPI development.展开更多
In the case of dry powder inhalation systems(DPIs),the development of carrierfree formulations has gained increased attention.Thereby,spray-drying is a promising technology and is widely used to produce carrier-free D...In the case of dry powder inhalation systems(DPIs),the development of carrierfree formulations has gained increased attention.Thereby,spray-drying is a promising technology and is widely used to produce carrier-free DPIs.Numerous works have been published about the co-spray-drying of active ingredients with various solid excipients and their effect on the physicochemical characteristics and aerodynamic properties of the formulations.However,only a few studies have been reported about the role of the solvents used in the stock solutions of spray-dried formulations.In the present work,DPI microcomposites containing ciprofloxacin hydrochloride were prepared by spray-drying in the presence of different ethanol concentrations.The work expresses the roughness,depth and width of the dimples for particle size as a novel calculation possibility,and as a correlation between the MMAD/D_(0.5)ratio and correlating it with cohesion work,these new terms and correlations have not been published–to the best of our knowledge–which has resulted in gap-filling findings.As a result,different proportions of solvent mixtures could be interpreted and placed in a new perspective,in which the influence of different concentrations of ethanol on the habit of the DPI formulations,and thus on in vitro aerodynamic results.Based on these,it became clear why we obtained the best in vitro aerodynamic results for DPI formulation containing 30%ethanol in the stock solution.展开更多
Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prep...Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.展开更多
The formulation and device collectively constitute an inhalation drug product.Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical...The formulation and device collectively constitute an inhalation drug product.Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical performance and usability of the product to improve patient compliance with treatment instruction.From the points of formulation,device and patient use,this article summarizes the inhalation drugs,including pressurized metered dose inhaler(pMDI),dry powder inhaler(DPI),and nebulizer that are currently available in the US and UK markets.It also discusses the practical considerations for the development of inhalers and provides an update on the corresponding regulations of the FDA(U.S.Food and Drug Administration)and the EMA(European Medicines Agency).展开更多
Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“...Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.展开更多
Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique s...Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.展开更多
Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothes...Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years;48 males and 5 females;GOLD 1/2/3/4 = 19/27/6/1;mMRC 0/1/2/3/4 = 14/22/12/4/1;UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.展开更多
The preparation of ultra-fine particles of salbutamol sulphate （SS） was accomplished with a reactive precipitation pathway, in which salbutamol and sulphuric acid were Used as reactants with the solvents of ethanol....The preparation of ultra-fine particles of salbutamol sulphate （SS） was accomplished with a reactive precipitation pathway, in which salbutamol and sulphuric acid were Used as reactants with the solvents of ethanol.The effects of sulphuric acid concentration, reaction temperature, stirring rate, and reaction time onthesize of the particle were investigated. A binary mixture composed of lactose and SS was prepared to evaluate SS. The results showed that ultra-fine SS particles with controlled diameters ranging between 3 μm and 0.8 μm and with a narrow distribution could be achieved. The morphology consisting of clubbed particles wassuccess.fully obtained. The purity of the particles reached above 98% with-UV detection. The dose- of dry powder inhalation was obtained by blending the particles with recrystallized lactose, which acted as a carrier. The deposition quantity of the drug in breathing tract was estimated using a twin imPinger apparatus. Compared with the Shapuer powder （purchased in the market）, the results showed that SS_particles had more quantifies.subsided in simulative lung.. _展开更多
In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various proc...In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.展开更多
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
基金the Wenzhou Basic Medical and Health Science and Technology Project,No.Y20210307.
文摘BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.
基金This work was supported by the National Natural Science Foundation of China(No.:81173002)the National Science and Technology Support Program(No.:2012BAI35B02).
文摘The purpose of this study was to investigate the spray dried lactose as carrier for dry powder inhalation(DPI).The lactose particles were prepared by spray drying,then the particle size,shape and crystal form were characterized by laser diffraction,scanning electron microscopy(SEM),X-ray diffraction(XRD)and differential scanning calorimetry(DSC).The spray dried lactose particles were spherical and amorphous,but would transfer to crystal form when storage humidity was above 32%.Thus,the humidity of the storage environment should be controlled below 30%strictly in order to maintain the amorphous nature of spray dried lactose which is a great benefit to DPI development.
基金supported by the UNKP-19–3-SZTE New National Excellence Program of the Ministry for Innovationthe EFOP-3.6.2-16-2017-00006‘LIVE LONGER—Development of Modern Medical Diagnostic Procedures and Therapies in a Translational Approach:from a Laboratory to a Patient Bed’project+1 种基金by the EFOP 3.6.3-VEKOP-16–2017–00009 projectwithin the CEEPUS CIII-RS-1113 short-term student mobility scholarship at the University of Graz,Austria。
文摘In the case of dry powder inhalation systems(DPIs),the development of carrierfree formulations has gained increased attention.Thereby,spray-drying is a promising technology and is widely used to produce carrier-free DPIs.Numerous works have been published about the co-spray-drying of active ingredients with various solid excipients and their effect on the physicochemical characteristics and aerodynamic properties of the formulations.However,only a few studies have been reported about the role of the solvents used in the stock solutions of spray-dried formulations.In the present work,DPI microcomposites containing ciprofloxacin hydrochloride were prepared by spray-drying in the presence of different ethanol concentrations.The work expresses the roughness,depth and width of the dimples for particle size as a novel calculation possibility,and as a correlation between the MMAD/D_(0.5)ratio and correlating it with cohesion work,these new terms and correlations have not been published–to the best of our knowledge–which has resulted in gap-filling findings.As a result,different proportions of solvent mixtures could be interpreted and placed in a new perspective,in which the influence of different concentrations of ethanol on the habit of the DPI formulations,and thus on in vitro aerodynamic results.Based on these,it became clear why we obtained the best in vitro aerodynamic results for DPI formulation containing 30%ethanol in the stock solution.
文摘Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.
文摘The formulation and device collectively constitute an inhalation drug product.Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical performance and usability of the product to improve patient compliance with treatment instruction.From the points of formulation,device and patient use,this article summarizes the inhalation drugs,including pressurized metered dose inhaler(pMDI),dry powder inhaler(DPI),and nebulizer that are currently available in the US and UK markets.It also discusses the practical considerations for the development of inhalers and provides an update on the corresponding regulations of the FDA(U.S.Food and Drug Administration)and the EMA(European Medicines Agency).
基金supported by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-D-202002)Scientific Research Project of Tianjin Municipal Education Commission (No.2019KJ083)
文摘Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.
基金the funding support for this study from GEA-NUS PPRL (N-148-000-008-001)SERC Grant No. 102 169 0049 (R-148-000-157-305)partial support from the NSF through the NNIN program
文摘Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.
文摘Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years;48 males and 5 females;GOLD 1/2/3/4 = 19/27/6/1;mMRC 0/1/2/3/4 = 14/22/12/4/1;UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.
基金Supported by the National High Technology Research and Development Program of China （2001AA218061） and the National Natural Science Foundation of China （20236020）.
文摘The preparation of ultra-fine particles of salbutamol sulphate （SS） was accomplished with a reactive precipitation pathway, in which salbutamol and sulphuric acid were Used as reactants with the solvents of ethanol.The effects of sulphuric acid concentration, reaction temperature, stirring rate, and reaction time onthesize of the particle were investigated. A binary mixture composed of lactose and SS was prepared to evaluate SS. The results showed that ultra-fine SS particles with controlled diameters ranging between 3 μm and 0.8 μm and with a narrow distribution could be achieved. The morphology consisting of clubbed particles wassuccess.fully obtained. The purity of the particles reached above 98% with-UV detection. The dose- of dry powder inhalation was obtained by blending the particles with recrystallized lactose, which acted as a carrier. The deposition quantity of the drug in breathing tract was estimated using a twin imPinger apparatus. Compared with the Shapuer powder （purchased in the market）, the results showed that SS_particles had more quantifies.subsided in simulative lung.. _
基金The Finnish Cultural Foundation and The Emil Aaltonen Foundation for the financial support.
文摘In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.
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.
