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1.
The aim of the present investigation was to prepare and evaluate the influence of adding fines on the in vitro performance of liposomal amikacin dry powder inhaler (AMK LDPI) formulations. Liposomes composed of hydrogenated soyaphosphatidylcholine, cholesterol and saturated soyaphosphatidylglycerol (AMK 1), or stearylamine (AMK 2) were prepared by a reverse phase evaporation technique, extruded to reduce size and separated from unentrapped drug. Purified liposomal dispersion was subjected to lyophilization using optimized cryoprotectant to achieve maximum percentage drug retentio (PDR). Lactose carrier in varying mass ratios with or without addition of fines in different mixing sequences was used to formulate AMK LDPI formulations. AMK LDPI formulations were characterized for angle of repose, compressibility index, dispersibility index, scanning electron microscopy, and fine perticle fraction (FPF). PDR was found to be 97.6%±2.2% for AMK1 and 98.5%±1.9% for AMK2 using sucrose as optimized cryoprotectant in lipid:sucrose ratio of 1∶4. Lactose carrier containing 10% fines (wt/wt) was found to be the optimum blend at 1∶5 mass ratio of liposome:lactose. The addition of fines and the order of mixing of fines were found to influence the FPF with significantly different device fractions. FPF of AMK LDPI formulations using Rotahaler as the delivery device at 30, 60, and 90 L/min were found to be 21.85%±2.2% and 24.6%±2.4%, 25.9% ±1.8% and 29.2%±2.1%, and 29.5%±2.6% and 34.2%±2.0% for AMK1 and AMK2, respectively. From the studies performed in this investigation, it was observed that liposomal charge, addition of fines and order of mixing fines, has a significant effect (P<.05) on in vitro deposition of drug from LDPI formulation.  相似文献   

2.
Purpose: Voriconazole has both low aqueous solubility and stability. We hypothesize that designing voriconazole in the form of a nano powder inhaler at a geometric diameter within 1–5?μm will enhance its stability and solubility. Therefore, we prepared nanoagglomerates of voriconazole which will collapse in the lungs to reform the nanoparticles.

Method: The nanoparticles were formulated using both stearic acid and sodium deoxycholate as edge activators. Osmogenic polycation polyethyleneimine (PEI) was used to form agglomerates of controllable size.

Results: Voriconazole nanoparticles and agglomerates showed a significant higher cumulative drug release than the pure powder (p?R2?=?0.95. Small-sized particles were formed (353?nm), while their zeta potential was ?30.7?mV. The agglomerates were 2.7?μm in size and their zeta potential was ?20.9?mV. The formation of porous agglomerates was confirmed using a transmission electron microscope. Cascade impactor was used to evaluate the aerodynamic properties of the nanoparticles and the agglomerates. The aerodynamic characterization of the nanoparticles and the agglomerates resulted in a significant smaller mass median aerodynamic diameter (MMAD) (p?p?p?p?Conclusion: The results suggest that using the combination of edge activators and diluted polycationic polymer solution provides porous voriconazole nanoagglomerates in a respirable range, which is proved successful in enhancing both the deposition and the dissolution of water insoluble-drugs in the lung.  相似文献   

3.
The purpose of the study was to prepare stable liposomally entrapped budesonide (BUD) for a dry powder inhaler (DPI) formulation. BUD liposomes composed of egg phosphatidyl choline and cholesterol were prepared by lipid film hydration technique and sonicated to have the desired size (<5 μm). A rapid method was used for separation of free drug by centrifugation at a lower centrifugal force (G value). Liposomal dispersion was subjected to lyophilization after blending BUD with cryoprotectant in varying bulk and mass ratios, and percent drug remaining entrapped after lyophilization was optimized. Comparative drug retention studies on storage of DPI formulations were carried out in accordance with International Conference on Harmonization guidelines. Critical relative humidity of the formulations was determined and reported as one of the manufacturing controls. Sucrose was found to be the most effective cryoprotectant when present on both sides of the lamellae of liposomes in a bulk strength of 500 mM and mass ratio of lipid:sugar; 1∶10. Blending of sorbolac before lyophilization showed better retention of encapsulated drug (95.59%). The respirable fraction of the product (20.69±1.50%) was comparable with that of the control (26.49±1.52%), suggesting that the liposomal BUD can be successfully delivered throughout the broncho-pulmonary tree. The findings demonstrate that liposome of BUD can be prepared with a high entrapment value, stabilized by lyophilization, and delivered as an aerosolized DPI. The stability studies of lyophilized product suggests a shelf-life of one year when stored under refrigeration (2°C–8°C).  相似文献   

4.
Aims: To determine the feasibility of formulating and aerosolizing powders containing bacteriophages KS4‐M and ΦKZ for lung delivery and treatment of pulmonary Burkholderia cepacia complex and Pseudomonas aeruginosa infections. Methods and Results: Endotoxin‐removed bacteriophages KS4‐M and ΦKZ were lyophilized in lactose/lactoferrin 60 : 40 w/w matrix and deagglomerated in a mixer mill (without beads) to formulate respirable powders. The powders were then aerosolized using an Aerolizer® capsule inhaler. Mass median aerodynamic diameter (MMAD) of this inhalable aerosol was determined using Andersen cascade impactor at 60 l min?1. Measured MMAD for both types of powders was 3·4 μm, and geometric standard deviation was 1·9–2·0. Viability of bacteriophages delivered distal to an idealized mouth‐throat replica was determined from bioassays of samples collected on filters placed after the idealized replica. As a percentage of inhaler load, amount of powder delivered distal to the mouth‐throat replica, which is a measure of lung delivery, was 33·7 ± 0·3% for KS4‐M and 32·7 ± 0·9% for ΦKZ. Titres collected downstream of the mouth throat were (3·4 ± 2·5) × 106 PFU for KS4‐M with an Aerolizer capsule load of (9·8 ± 4·8) × 106 and (1·9 ± 0·6) × 107 for ΦKZ with an Aerolizer capsule load of (6·5 ± 1·9) × 107. Conclusions: Bacteriophages KS4‐M and ΦKZ can be lyophilized without significant loss of viability in a lactose/lactoferrin 60 : 40 w/w matrix. The resulting powders can be aerosolized to deliver viable bacteriophages to the lungs. Significance and Impact of the Study: Development of lactoferrin‐based bacteriophage aerosol powders solidifies the ground for future research on developing novel formulations as an alternative to inhaled antibiotic therapy in patients with cystic fibrosis.  相似文献   

5.
The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% +/- 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 +/- 0.8 microm, maximum fine particle fraction (FPF) of 71.1 +/- 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 +/- 0.1 microm, and geometric standard deviation (GSD) 1.7 +/- 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi's Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection.  相似文献   

6.
The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (VIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery. Chitosan flakes were reduced in size using a cryo-milling technique. Milled powders were sieved between 45 and 125 μm aggregate sizes and characterized for particle size and distribution, morphology, and flow properties. Powders were blended in the micro-ball mill without the ball. Lyophilization followed by milling produced irregularly shaped, polydisperse particles with a median primary particle diameter of ≈21 μm and a yield of ≈37% of particles in the 45 to 125 μm particle size range. Flow properties of lactose and trehalose powders after lyophilization followed by milling and sieving were similar. Cryo-milling produced a small yield of particles in the desired size range (<10%). Lyophilization followed by milling and sieving produced particles suitable for nasal delivery with different physicochemical properties as a function of processing conditions and components of the formulation. Further optimization of particle size and morphology is required for these powders to be suitable for clinical evaluation. Published: March 10, 2006  相似文献   

7.
The purpose of this investigation was to evaluate the effect of mixing order and the influence of adding fines on in vitro performance of ipratropium bromide (ITB) dry powder inhaler formulations. Coarse lactose (CL) in varying mass ratio with or without addition of micronized lactose (ML) and ITB in different mixing sequences was used to formulate ternary mixtures. A binary mixture composed of CL and ITP served as control. The in vitro deposition of ITB from these formulations was measured using an Andersen cascade impactor (aerosolization at 39 L/min) employing a HandiHaler as the delivery device. It was observed that mixing order has a significant effect (P<.05) on in vitro deposition of ITB. Formulations with preblending of CL and ITB produced similar deposition profiles as the control, regardless of the added ML. In contrast, formulations without preblending resulted in significantly higher fine particle dose (FPD) as compared with the control. In addition, an increased quantity of ML generally resulted in an increase in drug deposition. The results show that the effect of ML on dispersion of ITB is highly dependent upon the mixing order. The evaluation of atomic force measurement (AFM) to forecast drug detachment and predict the aerodynamic characteristics resulted in similar attraction forces for the different pairs lactose/lactose (42.66±25.01 nN) and lactose/ITB (46.77±17.04 nN). Published: April 20, 2007  相似文献   

8.

Background

Dry powder dispersion devices offer potential for delivering therapeutic macromolecules to the pulmonary epithelia. Previously, freeze‐drying (lyophilisation) has been the accepted method for preparing dried formulations of proteins and non‐viral gene vectors despite the respirability of such powders being inadequate without further processing. In this study we compare the utility of freeze‐drying and spray‐drying, a one‐step process for producing dry and respirable powders, as methods for preparing non‐viral respiratory gene delivery systems.

Methods

Lipid:polycation:pDNA (LPD) vectors comprising 1,2‐dioleoyl‐3‐trimethylammoniumpropane (DOTAP), protamine sulphate and pEGFP‐N1 in 3% lactose solution were either snap‐frozen and lyophilised or spray‐dried. Lyophilised powder was used as recovered or following coarse grinding. Structural integrity of dehydrated pDNA was assessed by agarose gel electrophoresis and powder particle size determined by laser diffraction. The apparent structure of the systems was visualised by scanning and transmission electron microscopy with the biological functionality quantified in vitro (A549 human lung epithelial cell line) by Green Fluorescent Protein (GFP) associated fluorescence.

Results

Lyophilisation produced large, irregularly shaped particles prior to (mean diameter ~21 µm) and following (mean diameter ~18 µm) coarse grinding. Spray‐drying produced uniformly shaped spherical particles (mean diameter ~4 µm). All dehydrated formulations mediated reporter gene expression in A549 cells with the spray‐dried formulation generally proving superior even when compared with freshly prepared LPD complexes. Biological functionality of the LPD dry powders was not adversely affected following 3 months storage.

Conclusions

Spray‐drying has utility for producing stable, efficient and potentially respirable non‐viral dry powder systems for respiratory gene delivery. Copyright © 2002 John Wiley & Sons, Ltd.
  相似文献   

9.
Abstract

The motive behind present work was to discover a solution for overcoming the problems allied with a deprived oral bioavailability of salbutamol sulfate (SS) due to its first pass hepatic metabolism, shorter half-life, and systemic toxicity at high doses. Pulmonary delivery provides an alternative route of administration to avoid hepatic metabolism of SS, moreover facilitated diffusion and prolonged retention can be achieved by incorporation into liposomes. Liposomes were prepared by thin film hydration technique using 32 full factorial design and formulation was optimized based on the vesicle size and percent drug entrapment (PDE) of liposomes. Optimized liposomal formulation exhibited an average size of about 167.2?±?0.170?nm, with 80.68?±?0.74% drug entrapment, and 9.74?±?1.10?mV zeta potential. The liposomal dispersion was then spray dried and further characterized for in-vitro aerosol performance using Andersen Cascade Impactor. Optimized liposomal formulation revealed prolonged in-vitro drug release of more than 90% up to 14?h following Higuchi’s controlled release model. Thus, the proposed new-fangled liposomal formulation would be a propitious alternative to conventional therapy for efficient and methodical treatment of asthma and alike respiratory ailments.  相似文献   

10.
11.
This work aims to predict time courses of leaf area index (LAI) based on dry matter partitioning into the leaves and on specific leaf area of newly formed leaf biomass (SLA(n)) for year-round cut chrysanthemum crops. In five glasshouse experiments, each consisting of several plant densities and planted throughout the year, periodic destructive measurements were conducted to develop empirical models for partitioning and for SLA(n). Dry matter partitioning into leaves, calculated as incremental leaf dry mass divided by incremental shoot dry mass between two destructive harvests, could be described accurately (R(2 )= 0.93) by a Gompertz function of relative time, R(t). R(t) is 0 at planting date, 1 at the start of short-days, and 2 at final harvest. SLA(n), calculated as the slope of a linear regression between periodic measurements of leaf dry mass (LDM) and LAI, showed a significant linear increase with the inverse of the daily incident photosynthetically active radiation (incident PAR, MJ m(-2 )d(-1)), averaged over the whole growing period, the average glasshouse temperature and plant density (R(2 )= 0.74). The models were validated by two independent experiments and with data from three commercial growers, each with four planting dates. Measured shoot dry mass increase, initial LAI and LDM, plant density, daily temperature and incident PAR were input into the model. Dynamics of LDM and LAI were predicted accurately by the model, although in the last part of the cultivation LAI was often overestimated. The slope of the linear regression of simulated against measured LDM varied between 0.95 and 1.09. For LAI this slope varied between 1.01 and 1.12. The models presented in this study are important for the development of a photosynthesis-driven crop growth model for cut chrysanthemum crops.  相似文献   

12.
The purpose of this research was to investigate the effect of the shape of sodium salicylate (SS) particles on the physical properties as well as the in vitro aerosol performance of the granules granulated by the pressure swing granulation method. SS was pulverized with a jet mill (JM) to prepare the distorted particles, and SS aqueous solution was spray dried (SD) to prepare the nearly spherical particles. The particle size distribution, crushing strength, and pore size distribution of the granules were measured. The adhesive force of the primary particles in the granules was calculated according to Rumpf's equation. The in vitro aerosol performance of the granules was evaluated using a cascade impactor. Both JM and SD particles can be spherically granulated by the pressure swing granulation method without the use of a binder. The size of SD granules was smaller than that of JM granules. Although the crushing strength of the JM and SD granules is almost the same, the internal structures of JM granules and SD granules were found to differ, and the SD particles appear to have been condensed uniformly, resulting in a nearly spherical shape. In the inhalation investigation, the percentage of SS particles of appropriate size delivered to the region for treatment was noticeably higher for SD granules than for JM granules. This finding might be because the adhesive force of the SD primary particles was smaller than that of the JM primary particles in the granules and because the SD granules could be easily separated by air current to obtain the primary particles.  相似文献   

13.
The biofilm reactor has been frequently applied in wastewater treatment. The formation, structure and metabolic activity of the biofilms are closely associated with the detachment forces in the reactors. This paper reviews the essential role of detachment forces in the biofilm process. A more compact, stable and denser biofilm can be formed at a relatively higher detachment force. The detachment force has significant influence on the structure, mass transfer, production of exopolysaccharides, metabolic and genetic properties of the biofilm. In an engineering sense, the detachment forces can be manipulated, as a control parameter, to produce a more stable and compact biofilm for use in wastewater treatment. The molecular and genetic mechanisms responsible for the detachment force-associated phenomena are not yet fully understood.  相似文献   

14.
Water vapor adsorption isotherms were used for the estimation of surface areas and adsorption energy distribution functions of roots of barley grown at different pH levels and at a toxic Al level (10 mg·dm−3), induced at tillering and shooting stages of plants growth. Values of surface area as well as energy distributions were the same for the roots grown at all pH values studied: 2, 4 and 7 and not dependent on the age of the plants indicating that the protons do not alter the physicochemical build-up of the surface of roots. However, significant changes of the root surface properties under the influence of aluminum: increase of surface area, average adsorption energy and amount of highly energetic adsorption sites together with a decrease of low energetic sites were observed.  相似文献   

15.
Dry subtropical regions (DST), originally hosting woodlands and savannas, are subject to contrasting human pressures and land uses and different degrees of water limitation. We quantified how this variable context influences landscape pattern and vegetation functioning, by exploring the associations between three groups of variables describing (i) human pressures (population density, poverty, and market isolation) and climate (water availability), (ii) landscape pattern (woody cover, infrastructure, paddock size, etc.), and (iii) vegetation functioning (magnitude and stability of primary productivity), in regions of Asia, Africa, Australia, and America. We collected data from global socioeconomic databases and remote sensing products for 4525 samples (representing uncultivated and cultivated conditions), located along 35 transects spanning semiarid to subhumid conditions. A Reciprocal Averaging ordination of uncultivated samples revealed a dominant gradient of declining woody cover accompanied by lower and less stable productivity. This gradient, likely capturing increasing vegetation degradation, had a negative relationship with poverty (characterized by infant mortality) and with market isolation (measured by travel time to large cities). With partial overlaps, regions displayed an increasing degradation ranking from Africa to South America, to Australia, to North America, and to Asia. A similar analysis of cultivated samples, showed a dominant gradient of increasing paddock size accompanied by decreasing primary productivity stability, which included all regions except Asia. This gradient was negatively associated with poverty and population density. A unique combination of small paddocks and high infrastructure differentiated Asian cultivated samples. While water availability gradients were related to productivity trends, they were unrelated to landscape pattern. Our comparative approach suggests that, in DST, human pressures have an overwhelming role driving landscape patterns and one shared with water availability shaping vegetation functioning.  相似文献   

16.
以切花菊品种‘神马’(Chrysanthemum morifolium Ramat ‘Jinba’)为试材,于2010-2011年设计不同红光(R: (660 ±10) nm)与远红光(FR: (730±10)nm)比值(R/FR分别为0.5、2.5、4.5、6.5)的LED灯照射处理,研究不同R/FR值对温室切花菊形态指标、叶面积形成及干物质分配的影响。结果显示R/FR=2.5处理的植株叶片数、株高、茎粗、花径、叶面积及总干重均为各个处理中最高,R/FR=0.5处理的节间最长。所有R/FR处理的单株地上干物质重量与光质处理天数呈指数-线性模型。随处理天数的增加不同R/FR值处理菊花植株地上部分及地下部分干物质分配指数差异均不显著,叶片和花的干物质分配指数随处理天数的增加分别呈降低和升高的趋势,茎干物质分配指数则呈现先升高后降低的趋势,R/FR=2.5处理下,菊花叶片干物质分配指数和花干物质分配指数最高,而茎干物质分配指数却为最低;R/FR=6.5处理茎干物质分配指数最高,叶片干物质分配指数最低;0.5处理花朵干物质分配指数最低,说明远红光比例增加能够促进干物质向茎中分配,R/FR=2.5处理利于干物质向花朵中分配。  相似文献   

17.
Kennard  D. K.  Gholz  H. L. 《Plant and Soil》2001,234(1):119-129
We compared soil nutrient availability and soil physical properties among four treatments (high-intensity fire, low-intensity fire, plant removal, and harvesting gap) and a control (intact forest understory) over a period of 18 months in a tropical dry forest in Bolivia. The effect of treatments on plant growth was tested using a shade intolerant tree species (Anadenanthera colubrina Vell. Conc.) as a bioassay. Surface soils in high-intensity fire treatments had significantly greater pH values, concentrations of extractable calcium (Ca), potassium (K), magnesium (Mg), and phosphorus (P), and amounts of resin-available P and nitrogen (N) than other treatments; however, a loss of soil organic matter during high-intensity fires likely resulted in increased bulk density and strength, and decreased water infiltration rates. Low intensity fires also significantly increased soil pH, concentrations of extractable Ca, K, Mg, and P, and amounts of resin-available P and N, although to a lesser degree than high-intensity fires. Low-intensity fires did not lower soil organic matter contents or alter soil physical properties. Plant removal and harvesting gap treatments had little effect on soil chemical and physical properties. Despite the potentially negative effects of degraded soil structure on plant growth, growth of A. colubrina seedlings were greater following high-intensity fires. Evidently, the increase in nutrient availability caused by high-intensity fires was not offset by degraded soil structure in its effects on seedling growth. Long-term effects of high intensity fires require further research.  相似文献   

18.
干旱和湿润生境中主要优势树种叶片功能性状的比较   总被引:1,自引:0,他引:1  
以云南南部的沟谷雨林(湿润生境)和干热河谷萨瓦纳(savanna)稀树灌丛(干旱生境)中共31种主要优势木本植物为材料,研究了叶片主要功能性状单位面积叶干重(LMA)、单位干重氮含量(Nmass)和单位干重最大净光合速率(Amass)在2个生境中的差异及各性状间的关系。结果表明:在物种水平上,干旱和湿润生境中各树种的LMA值分别为46.88~178.63和45.35~93.16g·m-2;Amass值分别为48.12~176.65和71.38~265.76nmol·g-1·s-1;Nmass值分别为11.8~36.71和12.98~31.78mg·g-1;在群落水平上,干旱生境中LMA显著高于湿润生境,而Amass显著低于湿润生境,Nmass在2个生境中差异不显著;在群落尺度上,干旱生境中LMA与Nmass和Amass均呈显著负相关;在2生境中Nmass与Amass均呈显著正相关。同一生境下不同植物对环境的适应策略有差异,但各性状间的相关关系具有趋同性;从湿润到干旱生境,植物由快速生长转向以提高资源利用效率为主的适应策略。  相似文献   

19.
刘世荣 《生态学报》1999,19(4):534-542
通过将沙棘(HippophaerhamnoidesL.)与三种杨树品种(小黑杨(Populus‘Xiaohei’)昭林6号杨(P.‘Zaolin06’)和欧美杨64号(P.euramericanecv.‘N3016’)的人工林分别按株混和行混两种方式进行混交实验,研究了固氮植物沙棘对亚湿润干旱区的杨树人工林养分分布和循环的影响,连续3a的观测研究得以下结果,沙棘叶片的氮,磷和钾的元素粪土了高于杨树  相似文献   

20.
The geometric and energetic characteristics of root surfaces of two wheat (Triticum L.) varieties, Al tolerant (Inia 66/16) and Al sensitive (Henika), were estimated from experimental water vapor adsorption–desorption data. Roots stressed for around 1 week at pH 4 without and with a toxic aluminium level (0.741 mol m–3) were studied at the tillering and shooting stages. Roots grown continuously at pH 7 were taken as control. The surface properties of the pH 4 stressed roots were apparently the same as those of the control roots whatever the root age. For the roots of both varieties, the surface area and total micropore volume increased markedly after aluminium treatment. The average micropore radius increased significantly for the sensitive wheat, whereas it increased only slightly for the resistant one. Under Al treatment the number of large pores increased while small pores were fewer for both plants, indicating a possible alteration of the build-up of root tissue. The root surface pores were fractal. The fractal dimension of the sensitive wheat roots decreased under Al treatment, whereas for the resistant wheat this remained apparently unchanged. The adsorption energy distribution functions had different shapes for the sensitive and the resistant wheat varieties: the sensitive variety had greater number of high energy adsorption centers, which implies that the root tolerance on Al stress may be connected with lower polarity of the surface.  相似文献   

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