The Use of Electrohydrodynamic Spraying to Disperse Hydrophobic Compounds in Aqueous Media

Wu, Yun; Chalmers, Jeffrey J.; Wyslouzil, Barbara E.

doi:10.1080/02786820903012463

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…We refer to this supplement as solubilized cholesterol mixture (SCM). As discussed in more detail in our earlier work, 13 most of the cholesterol in the nanoparticles is solubilized by methyl‐β‐cyclodextrin, and higher, measureable cholesterol concentrations can be achieved in SCM than in NCM. For a typical SCM supplement, the cholesterol concentration was 730 ± 30 μg/mL before sterile filtration and 670 ± 17 μg/mL afterwards.…”

Section: Resultsmentioning

confidence: 85%

“…A detailed description of the method to produce nanoparticle cholesterol mixtures (NCM) by electrospray can be found in Wu et al (2009). 13 Briefly, to produce NCM supplements, cholesterol powder (Sigma C3045) was dissolved in 100% ethanol (Pharmco‐Aaper E200GP) at a concentration of 2 mg/mL. The mixture was delivered to a 27 gauge needle by a syringe pump at the flow rate of 2 mL/h.…”

Section: Methodsmentioning

confidence: 99%

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Enhanced productivity of NS0 cells in fed‐batch culture with cholesterol nanoparticle supplementation

Wyslouzil

et al. 2011

Biotechnology Progress

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NS0 cells are an important industrial cell line for the production of therapeutic monoclonal antibodies. Culturing these cells is challenging because they are cholesterol auxotrophs, and providing cholesterol to the cells is hampered by the low solubility of lipids in aqueous medium. Limited loading capacity, precipitation, instability, and toxicity are associated with traditional delivery methods that involve solvents or carrier molecules. In this work, nanoparticle cholesterol mixtures (NCM) were produced by electrohydrodynamic spraying and added directly to a cholesterol auxotroph NS0 cell line. Compared to a cholesterol-cyclodextrin solution and a commercial proprietary cholesterol solution, SyntheChol NS0 supplement, NCM is significantly less cytotoxic. In the fed batch cell culture process, product titer was increased by 32% when the NCM supplement replaced SyntheChol NS0 supplement. An even greater product titer improvement, 64%, was achieved when both NCM and SyntheChol NS0 supplements were used in the fed-batch process.

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Section: Resultsmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Enhanced productivity of NS0 cells in fed‐batch culture with cholesterol nanoparticle supplementation

Wyslouzil

et al. 2011

Biotechnology Progress

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“…Electrospray is used for dispersing hydrophobic compounds such as cholesterol, and demonstrated that when they are dispersed into aqueous solutions, they disperse faster and more efficiently in comparison to bulk mixing (Wu et al 2009) Most newly synthesized medicines, such as Taxol, are poorly soluble in water. Because of their poor solubility, a way to increase the solubility is to reduce the size of medicine particles and consequently increase the surface area of the particles, see Fig.…”

Section: Miscellaneous Applicationsmentioning

confidence: 99%

Producing Pharmaceutical Particles via Electrospraying with an Emphasis on Nano and Nano Structured Particles - A Review

Yurteri

Hartman

Marijnissen

2010

KONA

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Recent advances in nanotechnology offer nano sized or nanostructured pharmaceutical particles, being as small as the size of cells such as receptors or nucleic acids, which can be engineered to provide enhanced efficacy, solubility, or biocompatibility, and to administer at much lower dosages. However, industrial production of these particles is still challenging. Among different techniques, aerosol based ones might be favorable since they are considered as contamination free processes and do not interfere with complex molecules of drugs. We, in this review, consider liquid atomization, where droplet formation is followed by conversion into solid particles. The best candidate is a method, which not only produces mono sized droplets with a diameter smaller than the inside nozzle diameter but also generates small enough start up sizes. Such a method is found in: Electro-Hydrodynamic Atomization (EHDA) or Electrospraying. Electrospraying is now a well practiced technique for producing very fine monodisperse droplets from a liquid under the influence of electrical forces. By controlling the liquid flow rate and the electrostatic potential between the liquid and the counter electrode, droplets within a narrow size range can be generated, while the mean diameter ranges from nanometers up to several micrometers. Besides generating monodisperse droplets, electrosprays are also distinguished by their self dispersing nature due to Coulomb repulsion, the possibility of trajectory control of the produced charged droplets, and the reduced risk of nozzle clogging due to the large size of the orifice compared to the size of the droplets. We will discuss different spraying modes depending on the strength of the electric stresses relative to the surface tension stress on the liquid surface and on the inertia of the liquid leaving the nozzle. However, for the production of monodisperse nanoparticles the so called cone-jet mode will be explained in depth. Scaling laws can be used to estimate the operational conditions for producing nanodroplets of a certain size. Hartman and coworkers refined the scaling laws for EHDA in the Cone-Jet mode using theoretically derived models for the cone, jet, and droplet size. By means of several examples, a generic way to produce nanoparticles, via scaling laws, from a multitude of different precursors will be discussed. Several examples of medicine particles with different properties made by EHDA will be given. Processes based on bipolar coagulation, where oppositely charged carrier particles and nano sized active agents are brought together to form composite drugs, will be discussed. Finally some attention will be given to challenges on out-scaling of EHDA methods for industrial production.

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“…An important advantage of this technique is that biological materials, ß 2009 Wiley Periodicals, Inc. such as DNA (Chen et al, 2000;Davies et al, 2005), cells , proteins (Gomez et al, 1998;Pareta et al, 2005;Salata, 2005;Xie and Wang, 2007), and lipids (Wu et al, 2009a) can be electrosprayed without changing the biological activity of these materials; In contrast, more standard aerosolization techniques, such as nebulization, rapidly degrade delicate DNA (Davies et al, 2005).…”

Section: Introductionmentioning

confidence: 96%

Coaxial electrohydrodynamic spraying of plasmid DNA/polyethylenimine (PEI) polyplexes for enhanced nonviral gene delivery

Fei

Lee

et al. 2009

Biotech & Bioengineering

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DNA/polyethylenimine (PEI) polyplexes are an important class of nonviral vectors. Although the conventional preparation method, bulk mixing, is straightforward, the formation of the DNA/PEI polyplexes is not well controlled. This work explores coaxial electrohydrodynamic spraying (EHDS) as a novel, alternative method to produce DNA/PEI polyplexes in a more controlled manner. Both pGFP/PEI and pSEAP/PEI polyplexes were produced by EHDS with a coaxial needle setup. The size of the polyplexes was determined using dynamic light scattering, and their ability to transfect NIH 3T3 cells was observed by using an inverted fluorescence microscope (pGFP) or quantified by measuring the activity level of alkaline phosphatase (pSEAP). At nitrogen to phosphate ratio (N/P) of 6.7, the polyplexes produced by coaxial EHDS had delivery efficiencies up to 2.6 times higher than those produced by bulk mixing. The N/P ratio and the structure of the EHDS used to make the polyplexes were crucial factors in determining the delivery efficiency.

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The Use of Electrohydrodynamic Spraying to Disperse Hydrophobic Compounds in Aqueous Media

Cited by 12 publications

References 26 publications

Enhanced productivity of NS0 cells in fed‐batch culture with cholesterol nanoparticle supplementation

Enhanced productivity of NS0 cells in fed‐batch culture with cholesterol nanoparticle supplementation

Producing Pharmaceutical Particles via Electrospraying with an Emphasis on Nano and Nano Structured Particles - A Review

Coaxial electrohydrodynamic spraying of plasmid DNA/polyethylenimine (PEI) polyplexes for enhanced nonviral gene delivery

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