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Generation of Monodisperse Protein Nanoparticles by Electrospray Drying

Published online by Cambridge University Press:  15 February 2011

A. Gomez ,
D. Bingham ,
L. de Juan  and
K. Tang
A. Gomez
Affiliation:
Department of Mechanical Engineering, Yale University, P. O. Box 208286, New Haven, CT 06520-8286
D. Bingham
Affiliation:
Department of Mechanical Engineering, Yale University, P. O. Box 208286, New Haven, CT 06520-8286
L. de Juan
Affiliation:
Department of Mechanical Engineering, Yale University, P. O. Box 208286, New Haven, CT 06520-8286
K. Tang
Affiliation:
Department of Mechanical Engineering, Yale University, P. O. Box 208286, New Haven, CT 06520-8286
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Abstract

The feasibility of producing relatively monodisperse and biologically active protein particles by electrospray drying is demonstrated. The process entails dissolving dry powder in an electrosprayable solution. The solution is then dispersed and, after solvent evaporation, dry residues can be collected on suitable deposition substrates. The process was demonstrated in the case of insulin. Particles were sized visually, using a scanning electron microscope (SEM), and aerodynamically, using an inertial impactor. When electrosprays of nearly saturated solutions were operated in the stable cone-jet mode, impactor data showed that the particle average aerodynamic diameter ranged from about 88 to 110 nm in diameter and the distributions were quasi-monodisperse with relative standard deviation estimated at approximately 10%. SEM observations for the same conditions showed average particle dimensions ranging from 98 to 117 nm, with predominantly doughnut shapes. Smaller particles can be generated by decreasing the insulin concentration and/or by spraying smaller liquid flow rates. The biological activity of the electrospray-processed insulin samples was confirmed by comparing binding properties on insulin receptors against a control sample. Although the maximum production rate for monodisperse insulin nanoparticles from a single cone-jet is low, at about 0.23 mg/hour, overall production can be increased by multiplexing the device with microfabrication techniques.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 550: Symposium GG/HH/II – Biomedical Materials-Drug Delivery, Implants and Tissue Engr , 1998 , 101
Copyright
Copyright © Materials Research Society 1999

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References

1. Struyker-Boudier, H. A. J.. Ed. (1986) Rate-Controlled Drug Administration and Action, CRC Press, Boca Raton, Florida.Google Scholar
2. Gregoriadis, G., Senior, J. and Poste, G., Eds.(1986) Targeting of Drugs With Synthetic Systems, Plenum Press: New York.Google Scholar
3. Anderson, J. M., Kim, S. W., Kopecek, J. and Knutson, K., Eds. (1992) Advances in Drug Delivery Systems, Elsevier: New York.Google Scholar
4. Edelman, E. R., Brown, L. and Langer, R. (1996) Quantification of insulin release from implantable polymer-based delivery systems and augmentation of therapeutic effect with simultaneous release of somatostatin, J. Pharmaceutical Sci., 85, 1271–1275.Google Scholar
5. Wallace, B. M. and Lasker, J. S. (1993) Stand and Deliver: Getting Peptide Drugs into the Body”, Science, 260, 913–914.Google Scholar
6. Regan, S. L. (1991) Polymerized Liposomes as Drug Carriers in Polymers for Controlled Drug Delivery, Tarchia, P. T., Ed., CRC Press: Boca Raton, Florida.Google Scholar
7. Yeo, S.-D., Lim, G.-B., Debenedetti, P. G. and Bernstein, H. (1995) Formation of Microparticulate Protein Powders Using a Supercritical Fluid Antisolvent, Biotechnology and Bioengineering, 41, 341–346.Google Scholar
8. Couvreur, P. and Puisieux, F. (1993) Nano- and microparticles for the delivery of polypeptides and proteins, Advanced Drug Delivery Reviews, 10, 141–162.Google Scholar
9. Song, C. X. et al. (1997) Formulation and Characterization of Biodegradable Nanoparticles for Intravascular Local Drug Delivery, J. Control. Release, 43, 197–212.Google Scholar
10. Leroux, J., Allemann, E., Doelker, E. and Gurny, R. (1994) New Approach for the Preparation of nanoparticles by Emulsification-Diffusion Method, Eur. J. Pharm. Biopharm., 41, 14–18.Google Scholar
11. Mumumenthaler, M., Hsu, C. C. and Pearlman, R. (1994) Feasibility Study on Spray-Drying Protein Pharmaceuticals: Recombinant Human Growth Hormone and Tissue-type Plasminogen Activator, Pharmaceutical Research, 11, 12–20.Google Scholar
12. Bailey, A.G., Electrostatic Spraying of Liquids, Research Studies Press Ltd, UK, 1988.Google Scholar
13. Cloupeau, M. and Prunet-Foch, B. (1989) Electrostatic spraying of liquids in cone-jet mode, J. Electrostatics, 22, 135–159.Google Scholar
14. Loscertales, I. G. and Ferndindez de la Mora, J. (1993) in Synthesis and Characterization of Ultrafine Particles, Marijnissen, J. & Pratsinis, S., Ed., Delft University Press.Google Scholar
15. Chen, Da-ren, Pui, D.Y.H. and Kaufman, S. (1995) Electrospraying of conducting liquids for monodisperse aerosol generation in the 4nm to 1.8mm diameter range, J. Aerosol Sci., 26, 963–977.Google Scholar
16. Masters, K. (1991) Evaporation of Droplets Containing Dissolved Solids in Spray-Drying Handbook, 5th Edition, Longamn Scientific and Technical, Essex, UK, 329–330.Google Scholar
17. de Juan, L., Brown, S., Rosell, J., Serageldin, K., Lazcano, J. and Fernandez de la Mora, J.(1997) Electrostatic effects on inertial impactors J. Aerosol Science in press Google Scholar
18. Fernandez de la Mora, J. (1996) Drastic Improvement of the resolution of aerosol size spectrometers via aerodynamic focusing: The case of variable-pressure impactors. Chem. Eng. Corn. 151, 101–124.Google Scholar
19. Fernáindez de Ia Mora, J. and Loscertales, I. G. (1994) The current transmitted through an electrified conical meniscus, J. Fluid Mechanics, 260, 155–184.Google Scholar
20. Shapiro, D. L. et al. (1985) Insulin receptors and insulin effects on type II alveolar epithelial cells. Biophys. Biomed. Acta., 885, 216–220.Google Scholar
21. Brodie, I. and Spindtl, C. A. (1992) Advances in Electronics and Electron Physics, 83, 1–106.Google Scholar
22. Aguirre-de-Carcer, I. and de Ia Mora, J. Fernáindez (1995) Effect of the background gas on the current emitted from Taylor cones, J. Colloid and Interface Sciences.Google Scholar
23. Gomez, A., Bingham, D., de Juan, L. and Tang, K. (1998). Production of Protein Nanoparticles by Electrospray Drying, J. Aerosol Sci. 29, 561–574.Google Scholar