Abstract
Pulmonary delivery of proteins requires particles for delivery to be in the aerodynamic size range 1–5 μm for deep lung deposition. However, the traditional particle size reduction technique of jet-milling normally used for inhalation is not suitable for processing these protein particles because of their lability brought about by the weak physical interactions making up their higher order structures. Advanced techniques such as spray drying, spray freeze drying and the use of supercritical fluid technology have been developed to produce particles in the suitable size range and morphology for deep long deposition without altering the native conformation of these biomolecules. Judicious use of excipients and operating conditions are some of the factors needed for a successful particle design.
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References
1. Shoyele, S. A. and Slowey, A. (2006) Prospects of formulating protein/peptides as aerosols for pulmonary drug delivery. Int. J. Pharm. 314:1–8.
Shoyele, S. A, and Cawthorne, C. (2006) Particle engineering techniques for inhaled biopharmaceuticals. Adv. Drug Deliv. Rev. (in press).
3. Taylor, K. (2002) Pulmonary drug delivery, in Aulton, M. E. (ed.), Pharmaceutics, the Science of Dosage Form Design (). Churchill Livingston, Edinburgh, 473–498.
4. Okamoto, H., Todo, H., Lida, K., and Danjo, K. (2002) Dry powder for pulmonary delivery of peptides and proteins. KONA 20:71–83.
Lai, M. C and Topp, E. M. (1999) Solid state chemical stability of proteins and peptides. J. Pharm. Sci. 489–500.
Van Vlack, L. H. (1980) Elements of Material Science and Engineering, Addison Wesley, Reading, 185–208.
7. Hinrichs, W. L. J., De Smelt, N. N., Demeester, J., and Frijlink, H. W. (2005) Inulin is a promising cryo and lyoprotectant for PEGylated lipoplexes. J. Control. Rel. 103:465–479.
8. Johnson, K. A. (1997) Preparation of peptide and protein powder for inhalation,. Adv. Drug Del. Rev. 26:3–15.
9. Coldron, V., Vanderbist, F., Verbeeck, R., Mohammed, A., Lison, D., Preat, V., and Vanbever, R. (2003) Systemic delivery of parathyroid hormone (1–34) using inhalation dry powder in rats. J. Pharm. Sci. 92:938–950.
10. Sievers, R. E., Huang, E. T. S., Villa, J. A., Engling, G., Brauer, and P. R. (2003) Micronization of water-soluble or alcohol soluble pharmaceuticals and model compounds with a low temperature Bubble Dryer®. J. Supercritical Fluids 26:9–16.
11. Constantino, H. R., Firouzabadian, L., Hogeland, K., Wu, C., Banganski, C., Cordova, C. M., Carrasquillo, K. G., Griebenow, Zale, S. E., Tracy, W. A. (2000) Protein spray freeze drying. Effect of atomization conditions on particle size and stability. Pharm. Res. 17:1374–1384.
12. Zijlstra, G. S., Hinrichs, W. L. J., De Boer, A. H., and Frijlink, H. W. (2004) The role of particle engineering in relation to formulation and deaggragation principle in the development of a dry powder formulation of cetrorelix. Eur. J. Pharm. Sci. 23:139–149.
13. Yu, Z., Johnston, K. P., and Williams III, R. O. (2006) Spray freezing into liquid: Influence of atomization on protein aggregation and biological activity. Eur. J. Pharm. Sci. 27:9–18.
14. York, P. (1997) Strategies for particle design using supercritical fluid technologies. PSST 2:430–440.
15. Vemavarapu, C., Mollan, M. J., Lodaya, M., Needham, T. E. (2005) Design and process aspects of laboratory scale SCF particle formation system. Int. J. Pharm. 292:1–16.
16. Pasquali, I., Bettini, R., and Gordono, F. (2006) Solid state chemistry and particle engineering with supercritical fluids in pharmaceutics. Eur. J. Pharm. Sci. 27:299–310.
17. Tandya, A., Dehghani, F., and Foster, N. R. (2006) Micronization of cyclosporine using dense gas technique. J. Supercritical Fluids 27:272–278.
18. Yeo, S. D., Lim, G. B., Debenedetti, P. D., and Bernstein, H. (1993) Formation of microparticulate protein powder using a supercritical fluid anti-solvent. Biotechnol. Bioeng. 41:341–346.
Thiering, R., Dehghani, F., Foster, N. R. (2000) Micronization of model proteins using compressed CO2. Proceedings of the 5th International Symposium on Supercritical Fluids, Atlanta.
20. Yeo, S. D., Debenechi, P. G., Radosz, M., and Schmidt, H. W. (1993) Supercritical anti-solvent process for substituted para-linked aromatic polyamides: phase equilibrium and morphology study. Macromolecules 26:6207–6210.
21. Jovanovic, N., Bouchard, A., Hofland, G. W., Witkamp, G., and Crommelin, Jiskoot, W. (2004) Stabilization of proteins in dry powder formulation using supercritical fluid technology. Pharm. Res. 21:1955–1969.
22. Bodmeier, R., Wang, H., Dixon, D. J., Mawson, S., and Johnston, K. P. (1995) Polymeric microspheres prepared by spraying into compressed CO2. Pharm. Res. 12:1211–1217.
23. Lee, M. J., Kwon, J. –H., Shin, J. –S., and Kim, C. W. (2005) Microcrystallization of a-Lactalbumin, J. Crystal Growth 282:434–437.
24. Kwon, J. –H., Lee, B. –H., Lee, J. –J., and Kim, C. –W. (2004) Insulin microcrystal suspension as a long lasting formulation for pulmonary delivery. Eur. J. Pharm. Sci. 22:107–116.
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© 2008 Humana Press, a part of Springer Science + Business Media, LLC
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Shoyele, S.A. (2008). Engineering Protein Particles for Pulmonary Drug Delivery. In: Jain, K.K. (eds) Drug Delivery Systems. Methods in Molecular Biology™, vol 437. Humana Press. https://doi.org/10.1007/978-1-59745-210-6_7
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DOI: https://doi.org/10.1007/978-1-59745-210-6_7
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