A computer model for the clearance of insoluble particles from the tracheobronchial tree of the human lung

A multi-compartment model for the clearance of insoluble particles from the tracheobronchial tree of the human lung was created. As a significant innovation, the model considers specific mass transfer paths that may play an important role for slow bronchial clearance. These include the accumulation of particulate mass in the periciliary sol layer, an uptake of stored particles by airway macrophages, and the endocytosis of deposited mass by epithelial cells. Besides the gel layer representing fast mucociliary clearance, all cellular and extracellular units involved into the slow clearance process are described by respective compartments which are connected by specific transfer paths. The gastrointestinal tract (GIT), lymph nodes (LN), and blood capillaries are included into the model as final accumulation compartments, to which mass is transferred via the airway route and the transepithelial path. Besides a basic version of the model describing the whole tracheobronchial region by one set of compartments, also an advanced approach is introduced which, in accordance with the International Commission on Radiation Protection (ICRP), subdivides the conducting airways into a bronchial (BB) and bronchiolar (bb) part. Preliminary results were generated with MS-Excel from deposition data of 1-mummass median aerodynamic diameter (MMAD) particles, calculating local slow clearance fractions according to mathematical procedures introduced in previous publications. While mucociliary clearance is completely finished within 24h after exposure, slow clearance takes place in distinct phases and needs several days to weeks. This multi-stage event is also reflected in the respective retention curves which correspond well to previously published graphs.     

Particle agglomeration of chitosan–magnesium aluminum silicate nanocomposites for direct compression tablets

Exfoliated nanocomposites of chitosan-magnesium aluminum silicate (CS-MAS) particles are characterized by good compressibility but poor flowability. Thus, the aims of this study were to investigate agglomerates of CS-MAS nanocomposites prepared using the agglomerating agents water, ethanol, or polyvinylpyrrolidone (PVP) for flowability enhancement and to evaluate the agglomerates obtained as direct compression fillers for tablets. The results showed that the addition of agglomerating agents did not affect crystallinity, but slightly influenced thermal behavior of the CS-MAS nanocomposites. The agglomerates prepared using water were larger than those prepared using 95% ethanol because high swelling of the layer of chitosonium acetate occurred, allowing formation of solid bridges and capillary force between particles, leading to higher flowability and particle strength. Incorporation of PVP resulted in larger agglomerates with good flowability and high strength due to the binder hardening mechanism. The tablets prepared from agglomerates using water showed lower hardness, shorter disintegration times and faster drug release than those using 95% ethanol. In contrast, greater hardness and more prolonged drug release were obtained from the tablets prepared from agglomerates using PVP. Additionally, the agglomerates of CS-MAS nanocomposites showed good carrying capacity and provided desirable characteristics of direct compression tablets.     

Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide

The objective of this study was to compare the short-term respiratory effects due to the inhalation of electronic and conventional tobacco cigarette-generated mainstream aerosols through the measurement of the exhaled nitric oxide (eNO). To this purpose, twenty-five smokers were asked to smoke a conventional cigarette and to vape an electronic cigarette (with and without nicotine), and an electronic cigarette without liquid (control session).     

聚乙二醇对盐酸伊立替康脂质体体外释放及在不同稀释介质中稳定性的影响

目的:考察不同聚乙二醇含量对盐酸伊立替康脂质体体外释放特性及在不同稀释介质中稳定性的影响。方法:采用乙二胺四乙酸铵梯度法,以聚乙二醇2000含量分别为0、8、14、20、26 mg/ml的聚乙二醇2000-二硬脂酰磷脂酰乙醇胺(m PEG2000-DSPE)制备盐酸伊立替康脂质体,测定其包封率和粒径,评价其体外24 h内的累积释放度和在生理氯化钠溶液与5%葡萄糖注射液中的稳定性。结果:随着m PEG2000-DSPE含量的增加,盐酸伊立替康脂质体体外24 h累积释放度逐渐减小;以生理氯化钠溶液及5%葡萄糖注射液稀释后,随着m PEG2000-DSPE含量的增加,盐酸伊立替康脂质体的包封率和粒径变化均减小;当聚乙二醇2000质量浓度增加至20、26 mg/ml时,脂质体包封率和粒径基本不再变化。结论:m PEG2000-DSPE的加入可减慢盐酸伊立替康脂质体的体外释放,提高其在不同稀释介质中的稳定性。     

高密度脂蛋白颗粒大小及Gal-3、NT-proBNP水平预测冠心病介入治疗术后预后的临床价值

目的探究高密度脂蛋白(HDL)颗粒大小及半乳糖凝集素(Gal-3)、N末端脑钠肽前体(NT-proBNP)水平预测冠心病介入治疗术后预后的临床价值。方法选择132例于我院接受介入治疗的冠心病患者,均检测HDL颗粒大小、血清Gal-3、NT-proBNP水平,根据术后6个月预后分为预后良好组(104例)和预后不良组(28例),分析两组患者一般资料及检测结果差异,以受试者工作特征(ROC)曲线评价三个指标对预后的评估价值。结果预后不良组年龄高于预后良好组(P<0.05),合并糖尿症病例多于预后良好组(P<0.05),左室射血分数(LVEF)、高密度脂蛋白胆固醇(HDL-C)脂蛋白A-I(apoA-I)水平低于预后良好组(P<0.05),心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)水平高于预后良好组(P<0.05);预后不良组HDL颗粒大小、Gal-3、NT-proBNP水平显著高于预后良好组(P<0.05);经年龄、合并糖尿病、LVEF、cTnI、CK-MB水平的传统不良心血管事件危险因素校正后,logistics回归分析显示:高水平Gal-3、NT-proBNP是影响冠心病患者预后的独立危险因素(OR=2.067,8.365,P<0.05),HDL颗粒大小是影响冠心病患者预后的独立保护因素(OR=0.510,P<0.05);HDL颗粒大小、Gal-3、NT-proBNP水平评估冠心病患者预后截断值为0.89、14.77 ng/ml、589.6 pg/ml,敏感性分别为67.86%、78.00%及78.57%,特异性为64.42%、82.69%及75.96%;三者联合检测可获得更高检测效能。结论低水平的HDL颗粒大小及高水平Gal-3、NT-proBNP是影响冠心病患者介入治疗术后预后的独立危险因素,三者可用于患者术后预后评价,且联合诊断评估效能更高。     

齿科材料研磨粉尘粒径尺寸的相关研究

目的:对齿科三种不同材料研磨粉尘颗粒的尺寸进行检测及相关探讨。方法:制备齿科树脂、Vitallium金属及二氧化锆体瓷研磨粉尘各5mg,分别溶于50ml的75%酒精、丙酮及六偏磷酸钠溶液,形成悬液、制片,应用微分干涉相差显微镜(DIC)观察,对其粒径尺寸进行测量。结果:结果显示调磨后的三种齿科粉尘粒径尺寸均不相同,其中树脂粉尘颗粒的Dmax最大,为7.27μm,Dx约为4.46μm;二氧化锆体瓷的粉尘Dmax最小,其中Dmin仅为0.45μm,Dx为1.35μm;Vitallium金属粉尘颗粒的粒径位于二者之间,Dx约为3.67μm。结论:齿科三种不同材料研磨粉尘的粒径尺寸均不同,每种材料的粉尘粒径均小于10μm。由于齿科粉尘粒径较小,长期暴露于齿科粉尘环境下,可能会引起齿科医师肺组织的病变,建议临床医师加强自我防护。     

大蒜素降血脂作用及其机理研究

目的：探讨大蒜素的降血脂作用及其机理。方法：将50只昆明种小鼠随机分成5组，对照组、高脂饲料组（模型组）、大蒜素小、中、大剂量＋高脂饲料组。测定大蒜素对血清甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）以及低密度脂蛋白胆固醇（LDL-C）的影响。测定大蒜素对血清卵磷脂胆固醇脂酰基转移酶（LCAT）、心肌脂蛋白脂酶（LPL）、肝脂酶（HL）活性的影响以及体外对肝脏3-羟基-3-甲基戊二酰CoA（HMG-CoA）还原酶活性的影响。离体胆固醇微胶粒形成实验。结果：大蒜素明显降低喂以高脂饲料小鼠血清TC，TG及LDL-C水平，提高HDL-C含量，且作用与大蒜素剂量呈正相关。大蒜素在不同程度上可升高血清LCAT，心LPL和HL的活性，并在一定程度上降低肝脏HMG-CoA还原酶活性。大蒜素体外实验可抑制胆固醇微胶粒的形成。结论：大蒜素有显著的降血脂效应，其机理一方面可能是促进了脂蛋白之间的代谢与转化，另外可能是因为抑制了肠道胆固醇的吸收、减少了肝脏胆固醇的合成、促进了血清和肝脏甘油三酯的分解。     

Optimization of the aerosolization properties of an inhalation dry powder based on selection of excipients

The aim of this study was to investigate the influence of formulation excipients on physical characteristics of inhalation dry powders prepared by spray-drying. The excipients used were a series of amino acids (glycine, alanine, leucine, isoleucine), trehalose and dipalmitoylphosphatidylcholine (DPPC). The particle diameter and the powder density were assessed by laser diffraction and tap density measurements, respectively. The aerosol behaviour of the powders was studied in a Multi-Stage Liquid Impinger. The nature and the relative proportion of the excipients affected the aerosol performance of the powders, mainly by altering powder tap density and degree of particle aggregation. The alanine/trehalose/DPPC (30/10/60 w/w/w) formulation showed optimal aerodynamic behaviour with a mass median aerodynamic diameter of 4.7 μm, an emitted dose of 94% and a fine particle fraction of 54% at an airflow rate of 100 L/min using a Spinhaler inhaler device. The powder had a tap density of 0.10 g/cm³. The particles were spherical with a granular surface and had a 4 μm volume median diameter. In conclusion, optimization of the aerosolization properties of inhalation dry powders could be achieved by appropriately selecting the composition of the particles.     

Quality by design – Spray drying of insulin intended for inhalation

Quality by design (QBD) refers to a holistic approach towards drug development. Important parts of QBD include definition of final product performance and understanding of formulation and process parameters. Inhalation of proteins for systemic distribution requires specific product characteristics and a manufacturing process which produces the desired product. The objective of this study was to understand the spray drying process of insulin intended for pulmonary administration. In particular, the effects of process and formulation parameters on particle characteristics and insulin integrity were investigated. Design of experiments (DOE) and multivariate data analysis were used to identify important process parameters and correlations between particle characteristics. The independent parameters included the process parameters nozzle, feed, and drying air flow rate and drying air temperature along with the insulin concentration as a formulation parameter. The dependent variables included droplet size, geometric particle size, aerodynamic particle size, yield, density, tap density, moisture content, outlet temperature, morphology, and physical and chemical integrity. Principal component analysis was performed to find correlations between dependent and independent variables. Prediction equations were obtained for all dependent variables including both interaction and quadratic terms. Overall, the insulin concentration was found to be the most important parameter, followed by inlet drying air temperature and the nozzle gas flow rate. The insulin concentration mainly affected the particle size, yield and tap density, while the inlet drying air temperature mainly affected the moisture content. No change was observed in physical and chemical integrity of the insulin molecule.