Etoposide-loaded nanoparticles made from glyceride lipids: Formulation,characterization, in vitro drug release,and stability evaluation

The aim of the study was to prepare etoposide-loaded nanoparticles with glyceride lipids and then characterize and evaluate the in vitro steric stability and drug release characteristics and stability. The nanoparticles were prepared by melt emulsification and homogenization followed by spray drying of nanodispersion. Spray drying created powder nanoparticles with excellent redispersibility and a minimal increase in particle size (20–40 nm). Experimental variables, such as homogenization pressure, number of homogenization cycles, and surfactant concentration, showed a profound influence on the particle size and distribution. Spray drying of Poloxamer 407-stabilized nanodispersion lead to the formation of matrix-like structures surrounding the nanoparticles, resulting in particle growth. The in vitro steric stability test revealed that the lipid nanoparticles stabilized by sodium tauroglycocholate exhibit excellent steric stability compared with Poloxamer 407. All 3 glyceride nanoparticle formulations exhibited sustained release characteristics, and the release pattern followed the Higuchi equation. The spray-dried lipid nanoparticles stored in black polypropylene containers exhibited excellent long-term stability at 25°C and room light conditions. Such stable lipid nanoparticles with in vitro steric stability can be a beneficial delivery system for intravenous administration as long circulating carriers for controlled and targeted drug delivery. Published: September 30, 2005     

Size control of silica nanoparticles and their surface treatment for fabrication of dental nanocomposites

Nearly monodispersed silica nanoparticles having a controlled size from 5 to 450 nm were synthesized via a sol-gel process, and then the optimum conditions for the surface treatment of the synthesized silica nanoparticles with a silane coupling agent (i.e., 3-methacryloxypropyltrimethoxysilane (gamma-MPS)) were explored to produce dental composites exhibiting enhanced adhesion and dispersion of silica nanoparticles in the resin matrix. The particle size was increased by increasing amounts of the catalyst (NH4OH) and silica precursor (tetraethylorthosilicate, TEOS) and by decreasing the amount of water in the reaction mixtures regardless of solvents used for the synthesis. The particle size prepared by using ethanol as a solvent was significantly larger than that prepared by using methanol as a solvent when the composition of the reaction mixture was fixed. The nanosized particles in the 5-25 nm range were aggregated. The amount of grafted gamma-MPS on the surface of the synthesized silica nanoparticles was dependent on the composition of the reaction mixture when an excess amount of gamma-MPS was used. When surface treatment was performed at optimum conditions found here, the amount of the grafted gamma-MPS per unit surface area of the silica nanoparticles was nearly the same regardless of the particle size. Dispersion of the silica particles in the resin matrix and interfacial adhesion between silica particles and resin matrix were enhanced when surface treated silica nanoparticles were used for preparing dental nanocomposites.     

Gold@Silver@Gold Core Double-Shell Nanoparticles: Synthesis and Aggregation-Enhanced Two-Photon Photoluminescence Evaluation

A facile, straightforward, and low-cost method is proposed to synthesize gold@silver@gold core double-shell nanoparticles. The technique is a seed-mediated growth protocol that contains four steps of (1) gold seed synthesis, (2) gold seed growth, (3) silver layer coating through silver salt reduction, and (4) gold layer deposition via gold precursor reduction. The prepared nanoparticles had a narrow size distribution and the average particle size of 28 ± 1 nm. Cysteine was introduced to the nanoparticles solution as a coupling agent to assemble nanoparticles. Aggregation-induced two-photon photoluminescence enhancement of three types assembled nanoparticles, i.e., gold@silver@gold, gold@silver, and gold nanoparticles, was studied. It was observed that the assembled core double-shell nanoparticles presented huge enhancement in two-photon photoluminescence signal in comparison with two other nanoparticles. Moreover, the gold@silver@gold nanoparticle is a stable and biocompatible plasmonic nanosystem. This paper provides a novel candidate for two-photon photoluminescence excitation sensing and imaging for biomedical applications.

     

Determination of Fundamental Morphological Parameters of Supported Nanoparticle Ensembles

A new model to extract important morphological parameters of noble metal nanoparticle ensembles with a broad size and shape distribution is presented. The technique is based on a rigorous simulation of the inhomogeneously broadened extinction profiles of nanoparticle ensembles. As input data, only experimentally accessible parameters, such as the amount of deposited material, the nanoparticle number density, and the relative size distribution of the nanoparticles, are used. The model can be applied to oblate nanoparticles, which exhibit a strong correlation between their shape and size, e.g., to supported nanoparticles generated, for example, by deposition of atoms and subsequent nucleation or by gas phase deposition. Both methods are standard preparation techniques to generate well-defined nanoparticle ensembles under ultra high vacuum conditions. We apply our model to gold and silver nanoparticles on sapphire and TiO₂ supports and obtain a perfect agreement between the calculated and experimental data. More importantly, we could extract the functional dependence between the axial ratio and the radius of the nanoparticles within the ensemble and, therewith, the most probable axial ratio in the ensemble. In addition, the extinction spectrum of a nanoparticle ensemble irradiated with nanosecond pulsed laser light during growth has been successfully modeled. This demonstrates, that the model is able to describe shape changes of resonantly heated nanoparticles within the ensemble. By using the coverage as a free parameter, we could calculate from the extinction spectrum the average particle radius as well as the amount of desorbed atoms after irradiation with laser light. In summary, the model allows a fast, easy, but extensive morphological characterization of nanoparticle ensembles that exhibit a broad size and shape distribution.     

Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance

The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC > THF-URE > THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-012-9883-3) contains supplementary material, which is available to authorized users.Key words: aerodynamic diameter, cocrystal, spray drying, surface energy, theophylline     

Effect of formulation factors on incorporation of the hydrophilic peptide dalargin into PLGA and mPEG-PLGA nanoparticles

The objective of this study was to examine formulation factors that influence the incorporation of the hydrophilic peptide dalargin into poly(D, L-lactic-co-glycolic acid) (PLGA) and methoxy-polyethylene glycol (mPEG)-PLGA nanoparticles. In particular, the effect of ionic additives and nanoparticle method of preparation on the incorporation of dalargin and resultant nanoparticle properties was investigated. Biodegradable nanoparticles were prepared from mPEG-PLGA and PLGA by both solvent evaporation and solvent diffusion methods with inclusion of ionic additives of dextran sulphate (DS), sulfobutyl ether-beta-cyclodextrin (SB-CD), or sodium dodecyl sulfate (SDS). The resultant nanoparticles were analyzed for their mean particle size and size distribution, zeta-potential, peptide loading, yield, and morphology. The inclusion of ionic additives in the nanoparticle formulation significantly influenced dalargin entrapment efficiency (EE). For example, with the PLGA/SDS formulation EE increased from 13.3% to 91.2% and from 4.1% to 68.6% with the solvent diffusion and evaporation methods, respectively. The inclusion of ionic surfactant SDS has also lead to the formation of smaller size of nanoparticles. Isothermal titration microcalorimetry revealed a strong interaction between dalargin and DS, medium level interaction with SDS, and weak interaction with SB-CD. The results of this study suggest that a strong ionic interaction between peptides and additives may lead to enhanced peptide incorporation but also increased particle size. Intermediate ionic interaction, especially when it is associated with the formation of reversed micelles in a hydrophobic polymer solution, could be used to enhance the incorporation of hydrophilic peptides in PLGA and mPEG-PLGA nanoparticles.     

Production of nanoparticles using organisms

Recent developments in the biosynthesis of nanomaterials have demonstrated the important role of biological systems and microorganisms in nanoscience and nanotechnology. These organisms show a unique potential in environmentally friendly production and accumulation of nanoparticles with different shapes and sizes. Therefore, researchers in the field of nanoparticle synthesis are focusing their attention to biological systems. In order to obtain different applied chemical compositions, controlled monodispersity, desired morphologies (e.g., amorphous, spherical, needles, crystalline, triangular, and hexagonal), and interested particle size, they have investigated the biological mechanism and enzymatic process of nanoparticle production. In this review, most of these organisms used in nanoparticle synthesis are shown.     

Hard and Transparent Films Formed by Nanocellulose–TiO2 Nanoparticle Hybrids

The formation of hybrids of nanofibrillated cellulose and titania nanoparticles in aqueous media has been studied. Their transparency and mechanical behavior have been assessed by spectrophotometry and nanoindentation. The results show that limiting the titania nanoparticle concentration below 16 vol% yields homogeneous hybrids with a very high Young’s modulus and hardness, of up to 44 GPa and 3.4 GPa, respectively, and an optical transmittance above 80%. Electron microscopy shows that higher nanoparticle contents result in agglomeration and an inhomogeneous hybrid nanostructure with a concomitant reduction of hardness and optical transmittance. Infrared spectroscopy suggests that the nanostructure of the hybrids is controlled by electrostatic adsorption of the titania nanoparticles on the negatively charged nanocellulose surfaces.     

Endothelial nanoparticle binding kinetics are matrix and size dependent

Nanoparticles are increasingly important in medical research for application to areas such as drug delivery and imaging. Understanding the interactions of nanoparticles with cells in physiologically relevant environments is vital for their acceptance, and cell–particle interactions likely vary based on the design of the particle including its size, shape, and surface chemistry. For this reason, the kinetic interactions of fluorescent nanoparticles of sizes 20, 100, 200, and 500 nm with human umbilical vein endothelial cells (HUVEC) were determined by (1) measuring nanoparticles per cell at 37 and 4°C (to inhibit endocytosis) and (2) modeling experimental particle uptake data with equations describing particle attachment, detachment, and internalization. Additionally, the influence of cell substrate compliance on nanoparticle attachment and uptake was investigated. Results show that the number of binding sites per cell decreased with increasing nanoparticle size, while the attachment coefficient increased. By comparing HUVEC grown on either a thin coating of collagen or on top of three‐dimensional collagen hydrogel, nanoparticle attachment and internalization were shown to be influenced significantly by the substrate on which the cells are cultured. This study concludes that both particle size and cell culture substrate compliance appreciably influence the binding of nanoparticles; important factors in translating in vitro studies of nanoparticle interactions to in vivo studies focused on therapeutic or diagnostic applications. Biotechnol. Bioeng. 2011;108: 2988–2998. © 2011 Wiley Periodicals, Inc.     

Protein adsorption onto nanoparticles induces conformational changes: Particle size dependency,kinetics, and mechanisms

The use of nanomaterials in bioapplications demands a detailed understanding of protein–nanoparticle interactions. Proteins can undergo conformational changes while adsorbing onto nanoparticles, but studies on the impact of particle size on conformational changes are scarce. We have shown that conformational changes happening upon adsorption of myoglobin and BSA are dependent on the size of the nanoparticle they are adsorbing to. Out of eight initially investigated model proteins, two (BSA and myoglobin) showed conformational changes, and in both cases this conformational change was dependent on the size of the nanoparticle. Nanoparticle sizes ranged from 30 to 1000 nm and, in contrast to previous studies, we attempted to use a continuous progression of sizes in the range found in live viruses, which is an interesting size of nanoparticles for the potential use as drug delivery vehicles. Conformational changes were only visible for particles of 200 nm and bigger. Using an optimized circular dichroism protocol allowed us to follow this conformational change with regard to the nanoparticle size and, thanks to the excellent temporal resolution also in time. We uncovered significant differences between the unfolding kinetics of myoglobin and BSA. In this study, we also evaluated the plausibility of commonly used explanations for the phenomenon of nanoparticle size‐dependent conformational change. Currently proposed mechanisms are mostly based on studies done with relatively small particles, and fall short in explaining the behavior seen in our studies.     

Development of a chitosan-based nanoparticle formulation for delivery of a hydrophilic hexapeptide, dalargin

Nanoparticle based delivery systems can offer opportunities for targeting, controlled release, and enhanced stability of their drug, protein, or gene therapy payload. This study investigated the use of chitosan in combination with the ionic additives sulfobutyl-ether-7-beta-cyclodextrin (SB-CD) or SB-CD/dextran sulfate (SB-CD/DS) mixture in comparison with chitosan: DS in the formulation of nanoparticles incorporating the hexapeptide dalargin. The physical characteristics (particle size, zeta potential), entrapment and loading efficiency, and release of dalargin were quantified. It was demonstrated that anionic cyclodextrin, SB-CD, can be used in complex coacervation with chitosan, with and without the presence of DS, to form nanoparticles. The presence of SB-CD or DS in the nanoparticle formulation and the weight ratio of chitosan to anionic additive(s) influenced the physical properties of the nanoparticles and their ability to carry dalargin. In addition, the particle size of nanoparticles was also affected by the molecular weight of chitosan and DS. The use of either DS or SB-CD/DS mixture produced chitosan nanoparticles with small particle size, high dalargin entrapment efficiency, enhanced peptide stability, and sustained release characteristics.     

Computational design of Phe-Tyr dipeptide and preparation,characterization, cytotoxicity studies of Phe-Tyr dipeptide loaded PLGA nanoparticles for the treatment of hypertension

Phe-Tyr dipeptide which was investigated in Wakame food with greatest ACE-inhibitory activity is used as a pharmaceutical drug for the treatment of hypertension, cardiovascular diseases, and diabetic nephropathy. To improve the bioavailability of Phe-Tyr, a delivery system based on poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Phe-Tyr (Phe-Tyr-PLGA NPs) for treating hypertension and cardiovascular diseases was prepared in this study. In the experiments, poly(lactic-co-glycolic acid) (PLGA) and Phe-Tyr dipeptide-loaded PLGA nanoparticles were prepared using the double emulsion (w/o/w) method. The characterizations of the nanoparticles were performed with a UV–vis spectrometer, the Zeta-sizer system, and FTIR spectrometer. The optimum size of the Phe-Tyr dipeptide-loaded PLGA nanoparticle was obtained with a 213.8 nm average particle size, and a 0.061 polydispersity index, ?19.5 mV zeta potential, 34% of loaded and 90.09% of encapsulation efficiency. From TEM analysis, it was clearly seen that the dipeptide loaded nanoparticles had the spherical and non-aggregated morphology and Phe-Tyr dipeptide loaded-PLGA nanoparticles were obtained successfully. Cell toxicity of nanoparticles at different concentrations was assayed with XTT methods on L929 fibroblast cells. This study determined that the nanoparticles have low toxicity at lower concentration and toxicity augmented with increasing concentration of dipeptide. To analyze the effect of solvents on structure of Phe-Tyr, Molecular dynamics simulation was performed with GROMACS program and molecular orbital calculations were carried out to obtain structural and electronic properties of dipeptide. Moreover, molecular docking calculations were also employed to model and predict protein–drug interactions.     

Preparation of Silica Nanoparticles Through Microwave-assisted Acid-catalysis

Microwave-assisted synthetic techniques were used to quickly and reproducibly produce silica nanoparticle sols using an acid catalyst with nanoparticle diameters ranging from 30-250 nm by varying the reaction conditions. Through the selection of a microwave compatible solvent, silicic acid precursor, catalyst, and microwave irradiation time, these microwave-assisted methods were capable of overcoming the previously reported shortcomings associated with synthesis of silica nanoparticles using microwave reactors. The siloxane precursor was hydrolyzed using the acid catalyst, HCl. Acetone, a low-tan δ solvent, mediates the condensation reactions and has minimal interaction with the electromagnetic field. Condensation reactions begin when the silicic acid precursor couples with the microwave radiation, leading to silica nanoparticle sol formation. The silica nanoparticles were characterized by dynamic light scattering data and scanning electron microscopy, which show the materials'' morphology and size to be dependent on the reaction conditions. Microwave-assisted reactions produce silica nanoparticles with roughened textured surfaces that are atypical for silica sols produced by Stöber''s methods, which have smooth surfaces.     

Solution properties of starch nanoparticles in water and DMSO as studied by dynamic light scattering

Solution properties of starch nanoparticles dispersed in DMSO and in water were studied using dynamic light scattering. The particle size distribution had two main peaks in both solvents at all scattering angles studied. They were at around 40 and 300 nm, ascribed to isolated starch nanoparticles and their aggregates, respectively. From the excess scattering intensity by the 40-nm particles, the molecular weight of the nanoparticle was estimated as 2.2–2.6×10⁶ g/mol. When the concentration was increased, another peak appeared at around 1 μm. Raising the temperature from 25 to 65 °C did not change the distribution, indicating a purely entropic process in dynamic equilibrium of the aggregation. In DMSO, an oscillatory behavior was observed in the autocorrelation function at high temperatures.     

Biological synthesis of gold nanoparticles using Magnolia kobus and Diopyros kaki leaf extracts

Leaf extracts of two plants, Magnolia kobus and Diopyros kaki, were used for ecofriendly extracellular synthesis of metallic gold nanoparticles. Stable gold nanoparticles were formed by treating an aqueous HAuCl₄ solution using the plant leaf extracts as reducing agents. UV–visible spectroscopy was used for quantification of gold nanoparticle synthesis. Only a few minutes were required for >90% conversion to gold nanoparticles at a reaction temperature of 95 °C, suggesting reaction rates higher or comparable to those of nanoparticle synthesis by chemical methods. The synthesized gold nanoparticles were characterized with inductively coupled plasma spectrometry (ICP), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR), and particle analysis using a particle analyzer. SEM and TEM images showed that a mixture of plate (triangles, pentagons, and hexagons) and spherical structures (size, 5–300 nm) were formed at lower temperatures and leaf broth concentrations, while smaller spherical shapes were obtained at higher temperatures and leaf broth concentrations.     

Thermoluminescence of mercaptoethanol‐capped ZnS:Mn nanoparticles

The thermoluminescence (TL) of nanoparticles has become a matter of keen interest in recent times but is rarely reported. This article reports the synthesis of ZnS:Mn nanocrystals using a chemical route, with mercaptoethanol (ME) as the capping agent. The particle sizes for the nanocrystals were measured by X‐ray diffraction (XRD) and also by studying transmission electron microscopy (TEM) patterns. The particle sizes of the synthesized samples were found to be between 1 and 3 nm. For samples with different concentrations of the capping agent, it was found that the TL intensity of the ZnS:Mn nanoparticles increased as the particle size decreased. A shift in the peak position of the TL glow curve was also seen with decreasing particle size. The TL intensity was found to be maximal for samples with 1.2% of Mn. A change in the peak position was not found for samples with different concentrations of Mn. The half‐width glow peak curve method was used to determine the trap‐depth. The frequency factor of the synthesized samples was also calculated. The stability of the charge carriers in the traps increases with decreasing nanoparticle size. The higher stability may be attributed to the higher surface/volume ratio and also to the increase in the trap‐depth with decreasing particle size. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of particle size on activation energy and peak temperature of the thermoluminescence glow curve of undoped ZnS nanoparticles

This paper reports the effect of particle size on the thermoluminescence (TL) of undoped ZnS nanoparticles. ZnS nanoparticles were prepared using a chemical precipitation method in which mercaptoethanol was used as the capping agent. The nanoparticles were characterized by X‐ray diffraction, field emission gun‐scanning electron microscopy and high‐resolution transmission electron microscopy. When the concentrations of mercaptoethanol used are 0, 0.005, 0.01, 0.015, 0.025, 0.040 and 0.060 M, the sizes of the nanoparticles are 2.86, 2.81, 2.69, 2.40, 2.10, 1.90 and 1.80 nm, respectively. Initially, the TL intensity of UV‐irradiated ZnS nanoparticles increases with temperature, attains a peak value I_m for a particular temperature T_m, and then decreases with further increases in temperature. The values of both I_m and T_m increase with decreasing nanoparticle size. Whereas the activation energy decreases slightly with decreasing nanoparticle size, the frequency factor decreases significantly as the nanoparticle size is reduced. The order of kinetics for the TL glow curve of ZnS nanoparticles is 2. Expressions are derived for the dependence of activation energy (E_a) and T_m on nanoparticle size, and good agreement is found between the experimental and theoretical results. Copyright © 2015 John Wiley & Sons, Ltd.     

The effect of cosolvents on the formulation of nanoparticles from low-molecular-weight poly(l)lactide

The aim of this study was to formulate nanoparticles from poly(l)lactide by a modified nanoprecipitation method. The main focus was to study the effect of cosolvent selection on the shape, size, formation efficiency, degree of crystallinity, x-ray diffraction (XRD) reflection pattern, and zeta potential value of the particles. Low-molecular-weight (2000 g/mol) poly(l)lactide was used as a polymer, and sodium cromoglycate was used as a drug. Acetone, ethanol, and methanol were selected as cosolvents. Optimal nanoparticles were achieved with ethanol as a cosolvent, and the formation efficiency of the particles was also higher with ethanol as compared with acetone or methanol. The particles formulated by ethanol and acetone appeared round and smooth, while with methanol they were slightly angular. When the volume of the inner phase was decreased during the nanoprecipitation process, the mean particle size was also decreased with all the solvents, but the particles were more prone to aggregate. The XRD reflection pattern and the degree of crystallinity were more dependent on the amount of the solvents in the inner phase than on the properties of the individual cosolvents. The zeta potential values of all the particle batches were slightly negative, which partially explains the increased tendency toward particle aggregation.     

Whole-Body Nanoparticle Aerosol Inhalation Exposures

Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σ_g < 2.5 ⁵. The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size ⁶, which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria ⁵.A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO₂ inhalation toxicology studies. Critical components: 1) novel nano-TiO₂ aerosol generator; 2) 0.5 m³ whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO₂ aerosols generated from bulk dry nano-TiO₂ powders (primary diameter of 21 nm, bulk density of 3.8 g/cm³) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m³). The mass (M) of the collected particles was determined as M = (M_post-M_pre), where M_preand M_post are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is sampling flowrate (m³/min), and t is the sampling time (minute). The chamber pressure, temperature, relative humidity (RH), O₂ and CO₂ concentrations were monitored and controlled continuously. Nano-TiO₂ aerosols collected on Nuclepore filters were analyzed with a scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analysis.In summary, we report that the nano-particle aerosols generated and delivered to our exposure chamber have: 1) steady mass concentration; 2) homogenous composition free of contaminants; 3) stable particle size distributions with a count-median aerodynamic diameter of 157 nm during aerosol generation. This system reliably and repeatedly creates test atmospheres that simulate occupational, environmental or domestic ENM aerosol exposures.     

Increased nanoparticle penetration in collagenase-treated multicellular spheroids

The extracellular matrix of solid tumors presents a transport barrier that restricts nanoparticle penetration, thereby limiting the efficacy of nano-sized delivery vehicles for cancer imaging and therapy. In this study, the effect of nanoparticle size and collagenase treatment on penetration of carboxylated polystyrene nanoparticles was systematically assessed in a multicellular spheroid model. Penetration of the nanoparticles into the spheroid core was limited to particles smaller than 100 nm. Collagenase treatment of spheroids resulted in significantly increased penetration of nanoparticles up to 100 nm with only a minor increase in particle penetration observed for particles larger than 100 nm. Collagenase was immobilized onto the surface of nanoparticles for site-specific degradation of ECM proteins. Collagenase-coated, 100 nm nanoparticles demonstrated a 4-fold increase in the number of particles delivered to the spheroid core compared with control nanoparticles. Thus, nanoparticle delivery to solid tumors may be substantially improved by the incorporation of ECM-modulating enzymes in the delivery formulation.