Process considerations related to the microencapsulation of plasmid DNA via ultrasonic atomization

An effective means of facilitating DNA vaccine delivery to antigen presenting cells is through biodegradable microspheres. Microspheres offer distinct advantages over other delivery technologies by providing release of DNA vaccine in its bioactive form in a controlled fashion. In this study, biodegradable poly(D,L-lactide-coglycolide) (PLGA) microspheres containing polyethylenimine (PEI) condensed plasmid DNA (pDNA) were prepared using a 40 kHz ultrasonic atomization system. Process synthesis parameters, which are important to the scale-up of microspheres that are suitable for nasal delivery (i.e., less than 20 μm), were studied. These parameters include polymer concentration; feed flowrate; volumetric ratio of polymer and pDNA-PEI (plasmid DNA-polyethylenimine) complexes; and nitrogen to phosphorous (N/P) ratio. PDNA encapsulation efficiencies were predominantly in the range 82-96%, and the mean sizes of the particle were between 6 and 15 μm. The ultrasonic synthesis method was shown to have excellent reproducibility. PEI affected morphology of the microspheres, as it induced the formation of porous particles that accelerate the release rate of pDNA. The PLGA microspheres displayed an in vitro release of pDNA of 95-99% within 30 days and demonstrated zero order release kinetics without an initial spike of pDNA. Agarose electrophoresis confirmed conservation of the supercoiled form of pDNA throughout the synthesis and in vitro release stages. It was concluded that ultrasonic atomization is an efficient technique to overcome the key obstacles in scaling-up the manufacture of encapsulated vaccine for clinical trials and ultimately, commercial applications.

Creation of protein loaded biodegradable microparticles via ultrasonic atomization suitable for nasal delivery

Improved biopharmaceutical delivery may be achieved via the use of biodegradable microspheres as delivery vehicles. Biodegradable microspheres offer the advantages of maintaining sustained protein release over time whilst simultaneously protecting the biopharmaceutical from degradation. Particle samples produced by ultrasonic atomization were studied in order to determine a feed stock capable of producing protein loaded poly-ε-caprolactone (PCL) particles suitable for nasal delivery (i.e., less than 20 μm). A 40 kHz atomization system was used with a 6 mm full wave atomization probe. The effect of solids percent, feed flow rate, volumetric ratio of the polymer stock to the protein stock, and protein concentration in the protein stock on particle size characteristics were determined. It was shown that feed stocks containing 100 parts of 0.5 or 1.0% w/v PCL in acetone with one part 100 mg ml -1 BSA and 15 mg ml -1 PVA produced particles with a mass moment diameter (D[4,3]) of 13.17 μm and 9.10 μm, respectively in addition to displaying high protein encapsulation efficiencies of 93 and 95%, respectively. The biodegradable PCL particles were shown to be able to deliver encapsulated protein in vitro under physiological conditions.

Straightforward biodegradable nanoparticle generation through megahertz-order ultrasonic atomization

Simple and reliable formation of biodegradable nanoparticles formed from poly-ε-caprolactone was achieved using 1.645 MHz piston atomization of a source fluid of 0.5% w/v of the polymer dissolved in acetone; the particles were allowed to descend under gravity in air 8 cm into a 1 mM solution of sodium dodecyl sulfate. After centrifugation to remove surface agglomerations, a symmetric monodisperse distribution of particles φ 186 nm (SD=5.7, n=6) was obtained with a yield of 65.2%. © 2006 American Institute of Physics.

Production of biodegradable nano and micro particles via ultrasonic atomization for biopharmaceutical delivery

Biopharmaceuticals have been shown to have low delivery and transformation efficiencies. To over come this, larger doses are administered in order to obtain the desired response which may lead to toxicity and drug resistance. This paper reports upon a continuous particle production method utilizing surface acoustic wave atomization to reliably produce micro and nanoparticles with physical characteristics to facilitate the cellular uptake of biopharmaceuticals. By producing particles of an optimal size for cellular uptake, the efficacy and specificity of drug loaded nanoparticles will be increased. Better delivery methods will result in dosage reduction (hence lower costs per dose), reduced toxicity, and reduced problems associated with multidrug resistance due to over dosing.

Studies on pneumatic atomization

A study of atomization has been made with an external mixing-type pneumatic atomizer. The drops were sampled on Vaseline-coated cells using a shutter arrangement and their sizes were measured under a microscope. The effects of liquid viscosity, liquid surface tension, liquid flow rate, air velocity, and nozzle angle on drop size have been studied. A model, which explains adequately the influence of various factors, has been proposed. This model predicts the values of average drop sizes over a wide range of operating conditions. The model also explains the data of other investigators who have used other kinds of pneumatic atomizers.

Thermally induced secondary atomization of droplet in an acoustic field

We study the thermal effects that lead to instability and break up in acoustically levitated vaporizing fuel droplets. For selective liquids, atomization occurs at the droplet equator under external heating. Short wavelength [Kelvin-Helmholtz (KH)] instability for diesel and bio-diesel droplets triggers this secondary atomization. Vapor pressure, latent heat, and specific heat govern the vaporization rate and temperature history, which affect the surface tension gradient and gas phase density, ultimately dictating the onset of KH instability. We develop a criterion based on Weber number to define a condition for the inception of secondary atomization. (C) 2012 American Institute of Physics. [doi:10.1063/1.3680257]

Spreading and atomization of droplets on a vibrating surface in a standing pressure field

We report the first observation and analytical model of deformation and spreading of droplets on a vibrating surface under the influence of an ultrasonic standing pressure field. The standing wave allows the droplet to spread, and the spreading rate varies inversely with viscosity. In low viscosity droplets, the synergistic effect of radial acoustic force and the transducer surface acceleration also leads to capillary waves. These unstable capillary modes grow to cause ultimate disintegration into daughter droplets. We find that using nanosuspensions, spreading and disintegration can be prevented by suppressing the development of capillary modes and subsequent break-up. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4757567]

AN EXPERIMENTAL STUDY ON EFFERVESCENT ATOMIZATION OF BIO-OIL FUELS

This paper presents the work on detailed characterization of effervescent spray of Jatropha and Pongamia pure plant oils. The spray characteristics of these biofuels are compared with those of diesel. Both macroscopic and microscopic spray characteristics at different injection pressures and gas-to-liquid ratio (GLR) have been studied. The particle/droplet imaging analysis (PDIA) technique along with direct imaging methods are used for the purpose of spray characterization. Due to their higher viscosity, pure plant oils showed poor atomization compared to diesel and a blend of diesel and pure plant oil at a given GLR. Pure plant oil sprays showed a lower spray cone angle when compared to diesel and blends at lower GLRs. However, the difference is not significant at higher GLRs. Droplet size measurements at 100 mm downstream of the exit orifice showed reduction in Sauter mean diameter (SMD) diameter with increase in GLR. A radial variation in the SMD is observed for the blend and pure plant oils. Pure oils showed a larger variation when compared to the blend. Spray unsteadiness has been characterized based on the image-to-image variation in the mean droplet diameter and fluctuations in the spray cone angle. Results showed that pure plant oil sprays are more unsteady at lower GLRs when compared to diesel and blend. A critical GLR is identified at which the spray becomes steady. The three regimes of spray operation, namely ``steady spray,'' ``pulsating spray,'' and ``spray and unbroken liquid jet'' are identified in the injection pressure-GLR parameter space for these pure plant oils. Two-phase flow imaging inside the exit orifice shows that for the pure plant oils, the flow is highly transient at low GLRs and the bubbly, slug, and annular two-phase flow regimes are all observed. However, at higher GLRs where the spray is steady, only the annular flow regime is observed.

Criteria for thermally induced atomization and catastrophic breakup of acoustically levitated droplet

We report thermally induced instability leading to catastrophic breakup in acoustically levitated vaporizing fuel droplets. Change in surface tension and viscosity with increase in droplet temperature causes wide fluctuations in droplet aspect ratio. If the viscous damping of aspect ratio oscillation is not strong enough, the droplet goes through unbounded stretching. If the droplet exceeds a critical Weber number locally, a bag type and capillary wave induced atomization can occur, which leads to catastrophic breakup. A stability criterion has been established based on the inhomogeneity of Bernoulli (acoustic) pressure and surface tension of the droplet in terms of a local Weber number and Ohnesorge number. This instability is thermally induced in a droplet which does not experience instabilities without heating. (C) 2012 Elsevier Ltd. All rights reserved.

Review on atomization and sprays of biofuels for IC engine applications

Ever increasing energy requirements, environmental concerns and energy security needs are strongly influencing engine researchers to consider renewable biofuels as alternatives to fossil fuels. Spray process being important in IC engine combustion, existing literature on various biofuel sprays is reviewed and summarized. Both experimental and computational research findings are reviewed in a detailed manner for compression ignition (CI) engine sprays and briefly for spark ignition (SI) engine sprays. The physics of basic atomization process of sprays from various injectors is included to highlight the most recent research findings followed by discussion highlighting the effect of physico-chemical properties on spray atomization for both biofuels and fossil fuels. Biodiesel sprays are found to penetrate faster and haw narrow spray plume angle and larger droplet sizes compared to diesel. Results of analytical and computational models are shown to be useful in shedding light on the actual process of atomization. However, further studies on understanding primary atomization and the effect of fuel properties on primary atomization are required. As far as secondary atomization is concerned, changes in regimes are observed to occur at higher air-jet velocities for biodiesel compared to those of diesel. Evaporating sprays revealed that the liquid length is longer for biodiesel. Pure plant oil sprays with potential use in CI engines may require alternative injector technology due to slower breakup as compared to diesel. Application of ethanol to gasoline engines may be feasible without any modifications to port fuel injection (PFI) engines. More studies are required on the application of alternative fuels to high pressure sprays used in Gasoline Direct Injection (GDI) engines.

Experimental studies on air-assisted impinging jet atomization

In the present study, a novel air-assisted impinging jet atomization is demonstrated. A configuration in which a gas jet is directed on to the impinging point of two liquid jets is used to improve the atomization. The effect of liquid properties such as viscosity and surface tension, angle between liquid jets and gas injection orifice diameter on spray characteristics has been experimentally studied. Backlit imaging and particle/droplet imaging and analysis techniques are utilized to characterize the sprays. The experimental results indicate that the effect of liquid viscosity is significant on the liquid sheet break up formed by the impinging jets. However, surface tension does not affect the spray structure significantly in this mode of atomization. At low liquid jet velocity, the prompt mode of atomization is observed where as atomization occurs in classical mode at higher liquid jet velocity. Results showed that variation in the angle between liquid jets do not affect the breakup phenomenon significantly. The spray angle is computed by finding the angle between the lines joining the impinging point and spray edge at an axial distance of 15 mm downstream of the impinging point from the ensemble-averaged data over 100 spray images. It was observed that effect of liquid jets impinging angle on the spray angle is higher at higher liquid velocity. Higher viscosity liquids exhibit lower spray angles. Droplet size measurements indicate a radial variation in the spray. An overall Sauter Mean Diameter (SMD) value is obtained by combining the droplet statistics at all radial locations at a fixed axial location. A very interesting trend is that the SMD is constant beyond a critical Gas to Liquid Ratio (GLR) and momentum ratio for a large variation in liquid viscosity and surface tension. This observation has important ramifications for fuel flexible systems. (C) 2013 Elsevier Ltd. All rights reserved.

Analysis on the atomization characteristics of aviation biofuel discharging from simplex swirl atomizer

The atomization characteristics of aviation biofuel discharging from a simplex swirl atomizer into quiescent atmospheric air are studied. The aviation biofuel is a mixture of 90% commercially available camelina-derived biofuel and 10% VonSol-53 (aromatics). The experiments are conducted in a spray test facility at varying fuel flow rate conditions. The measured characteristics include atomizer flow number, spray cone angle, breakup length of liquid sheet, wavelength of undulations on liquid sheet, and spray droplet size. The characteristics of biofuel sheet breakup are deduced from the captured images of biofuel spray. The measurements of spray droplet size distribution are obtained using Spraytec. The experimentally measured characteristics of the biofuel sheet breakup are compared with the predictions obtained from the liquid film breakup model proposed by Senecal et al. (1999). The measurements of wavelength and breakup length of the biofuel sheet discharging from the simplex swirl atomizer agree well with the model predictions. The model-predicted droplet size for the biofuel spray is significantly higher than the experimentally measured Sauter mean diameter (SMD). The spray droplets formed from the liquid sheet breakup undergo secondary atomization until 35-45 mm from the atomizer exit and thereafter the SMD increases downstream due to the combined effect of fuel evaporation and droplet coalescence. A good comparison is observed between the experimentally measured SMD of the biofuel spray and the predictions obtained using the empirical correlation reported in literature for sprays discharging from simplex swirl atomizers. (C) 2015 Elsevier Ltd. All rights reserved.