Abstract
In the last decades, development of products resulting from the application of molecular biology and biotechnology has demonstrated accelerated progress; as a result, the use of biological products such as proteins and enzymes has increased considerably in the food and pharmaceutical industry (Wanh 2000). Since most of these biomolecules, particularly enzymes, are extremely sensible to changes in temperature, pH, ionic force, and water concentration, scientists in these fields are in constant search of new methodologies and techniques to improve their stability. In industrial processes, biomolecules are obtained in aqueous solutions; however, in this medium their shelf life is relatively short. A remarkable improvement in the stability of protein based drugs has been obtained when these biomolecules are taken to a dry state; unfortunately, the freeze drying or spray-drying processes (which are the most common used techniques to obtain dry protein) expose these molecules to extreme conditions that cause a considerable decrease in their activity (Passot et al. 2005; Liao et al. 2004; Hinrichs et al. 2001; Heller et al. 1999).
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Abbreviations
- DSC:
-
Differential scanning calorimetry
- DTA:
-
Differential thermal analysis
- T g :
-
Glass transition temperatures
- T m :
-
Thermal stability
References
Angell A (1995) Formation of glasses from liquids and biopolymers. Science 267:1924–1935
Bell LN, Hageman MJ, Muraoka LM (1995) Thermally induced denaturation of lyophilized bovine somatotropin and lysozyme as impacted by moisture and excipients. J Pharm Sci 84:707–712
Buitink J, Van den Dries IJ, Hoekstra FA, Alberda M, Hemminga MA (2000) High critical temperature above T g may contribute to the stability of biological systems. Biophys J 79(2):1119–1128
Buitink J, Leprince O (2004) Glass formation in plant anhydrobiotes: survival in the dry state. Cryobiology 48:215–228
Buitink J, Leprince O (2008) Intracellular glasses and seed survival in the dry state. C R Biol 331(10):788–795
Carpenter JF, Crowe JH (1989) An infrared spectroscopic study of the interactions of carbohydrates with dried proteins. Biochemistry 28:3916–3922
Crowe LM (1984) Lessons from nature: the role of sugars in anhydrobiosis. Comp Biochem Physiol A 131:505–513
Crowe JH, Crowe LM, Womersley C, Mouradian R (1984) Preservation of functional integrity during long term storage of a biological membrane. Biochim Biophys Acta 778(3):615–617
Cueto M, Dorta MJ, Munguía O, Llabrés M (2003) New approach to stability assessment of protein solution formulations by differential scanning calorimetry. Int J Pharm 252:159–166
Duncan QM, Royal PG, Kett VL, Hopton ML (1999) The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems. Int J Pharm 179:179–207
Fox KC (1995) Putting proteins under glass. Science 267:1922–1923
Green JL, Angell CA (1989) Phase relations and vitrification in saccharide-water solutions and the trehalose anomaly. J Phys Chem 93:2880–2882
Grigera JR, Bolzicco V (2008) Molecular mobility and ageing of sugar glasses. Food Chem 106(4):1314–1317
Heller M, Carpenter J, Randolph T (1999) Protein formulation and lyophilization cycle design: prevention of damage due to freeze-concentration induced phase separation. Biotechnol Bioeng 63(2):166–174
Higl B, Kurtmann L, Carlsen CU, Ratjen J, Först P, Skibsted LH, Ulrich K, Risbo J (2007) Impact of water activity, temperature, and physical state on the storage stability of Lactobacillus paracasei ssp. Paracasei freeze-dried in a lactose matrix. Biotechnol Progr 23:794–800
Hinrichs WLJ, Prinsen MG, Frijlink HW (2001) Inulin glasses for the stabilization of therapeutic proteins. Int J Pharm 215:163–174
Liao Y-H, Brown MB, Martin GP (2004) Investigation of the stabilisation of freeze-dried lysozyme and the physical properties of the formulations. Eur J Pharm Biopharm 58:15–24
Liao Y-H, Brown M, Quader A, Martin GP (2002a) Protective mechanism of stabilizing excipients against dehydration in the freeze-drying of proteins. Pharm Res 19(12):1854–1861
Liao Y-H, Brown MB, Nazir T, Quader A, Martin GP (2002b) Effects of sucrose and trehalose on the preservation of the native structure of spray-dried lysozyme. Pharm Res 19(12):1847–1853
Lumry R, Eyring H (1954) Conformation changes of proteins. J Phys Chem 58:110–120
Lu J, Wang X-J, Liu Y-X, Ching C (2007) Thermal and FTIR investigation of freeze-dried protein-excipient mixtures. J Therm Anal Calorim 89(3):913–919
Martínez LM, Videa M, Mederos F, Mesquita J (2007) Constructing a high-sensitivity, computer-interfaced, differential thermal analysis device for teaching and research. J Chem Educ 84(7):1222–1223
Martínez LM, Videa M, Mesquita, J (2013) Design, construction and calibration of a portable multi sample DTA setup. Thermochim. Acta 560:89–94
Martínez LM, Videa M, Mederos F, de Moral Y (2011) Preservation effect of vitreous non reducing carbohydrates on the enzymatic activity, denaturation temperature and retention of native structure of Lysozyme. J Mex Chem Soc 55(3):185–189
Nath S, Satpathy GR, Mantri R, Deep S, Ahluwalia J (1998) Thermal stability of alcohol dehydrogenase enzyme determined by activity assay and calorimetry. Thermochim Acta 309:193–196
Nicholls H (2004) Cash injection for thermostable vaccines. Drug Discov Today 9(22):945
Ohtake S, Wang J (2011) Trehalose: current use and future applications. J Pharm Sci 100(6):2020–2053
Oliver AE, Leprince O, Wolkers WF, Hincha DK, Heyer AG, Crowe JH (2001) Non-disaccharide-based mechanisms of protection during drying. Criobiology 43(2):151–167
Passot S, Fonseca F, Alarcon-Lorca M, Rolland D, Marin M (2005) Physical characterisation of formulations for the development of two stable freeze-dried proteins during both dried and liquid storage. Eur J Pharm Biopharm 60(3):335–348
Patist A, Zoerb H (2005) Preservation mechanisms of trehalose in food and biosystems. Colloids Surf 40(2):107–113
Richards AB, Krakowka S, Dexter LB, Schmid H, Wolterbeek APM, Waalkens-Berendsen DH, Shigoyuki A, Kurimoto M (2002) Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol 40(7):871–898
Roos Y (1993) Melting and glass transitions of low molecular weight carbohydrates. Carbohydr Res 238:39–48
Sheri LS, Tang X, Chang L, Hancock BC, Pikal MJ (1999) Characterization of the time scales of molecular motion in pharmaceutically important glasses. J Phys Chem B 103(20):4113–4121
Sochava IV (1997) Heat capacity and thermodynamic characteristics of denaturation and glass transition of hydrated and anhydrous proteins. Biophys Chem 69:31–41
Sun WQ, Davison P, Chan HSO (1998) Protein stability in the amorphous carbohydrate matrix: relevance to anyhydrobiosis. Biochim Biophys Acta 1425:245–254
Wanh W (2000) Lyophilization and development of solid protein pharmaceuticals. Int J Pharm 203:1–60
Wolkers WF, Oliver A, Tablin F, Crowe JH (2004) Fourier-transform infrared spectroscopy study of sugar glasses. Carbohydr Res 339(6):1077–1085
Worrall EE, Litamoi JK, Seck BM, Ayelet G (2001) Xerovac: an ultra rapid method for the dehydration and preservation of live attenuated Rinderpest and Peste des Petits ruminants vaccines. Vaccine 19:834–839
Zografi G, Saleki-Gerhardt A (1994) Non-isotthermal crystallization of sucrose from amorphous state. Pharm Res 11(8):1166–1173
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Martínez, L.M., Videa, M., Mederos, F., de Moral, Y., Mora, M., Pérez, C. (2015). Phase Transitions in Sugars and Protein Systems: Study of Stability of Lysozyme in Amorphous Sugar Matrices. In: Gutiérrez-López, G., Alamilla-Beltrán, L., del Pilar Buera, M., Welti-Chanes, J., Parada-Arias, E., Barbosa-Cánovas, G. (eds) Water Stress in Biological, Chemical, Pharmaceutical and Food Systems. Food Engineering Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2578-0_22
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