The secondary structure and aggregation of lyophilized tetanus toxoid

Journal of Pharmaceutical Sciences
H R CostantinoR Langer

Abstract

Tetanus toxoid (TT), the vaccine for tetanus, is an important protein antigen and candidate for sustained release from polymeric matrices. During administration from the latter, the solid (e.g., lyophilized) protein will be exposed to elevated levels of temperature and moisture, conditions which trigger its aggregation. To examine the connection between this aggregation and the structure of the TT molecule in the solid state, Fourier-transform infrared (FTIR) spectroscopy was employed to determine the secondary structure of TT in the presence of various excipients. We found that excipient-free TT undergoes a significant alteration (mostly reversible) in the secondary structure during lyophilization. Specifically, more than half the total alpha-helix content was lost with a concomitant increase in beta-sheet structure. The extent of structural alterations in the presence of 1:5 (g:g protein) NaCl, sorbitol, or poly-(ethylene glycol), did not correlate with stability conferred towards moisture-induced aggregation. These results suggest that the degree of retention of the native protein structure in the dry state is not a general predictor of stability for the "wetted" solid within polymer controlled-release vehicles.

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Citations

Mar 7, 2002·International Journal of Pharmaceutics·Pierre O SouillacJ Howard Rytting
Sep 1, 2000·International Journal of Pharmaceutics·W Wang
Jul 8, 1998·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·S L ShamblinG Zografi
May 16, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Amber Clausi, Pierre Chouvenc
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Jun 3, 1998·Journal of Microencapsulation·S P SchwendemanR Langer
Jan 26, 2007·Journal of Pharmaceutical Sciences·Ahmad M Abdul-FattahMichael J Pikal
Jul 2, 2009·Journal of Pharmaceutical Sciences·Liuquan Lucy Chang, Michael J Pikal
Apr 25, 2007·Journal of Pharmaceutical Sciences·Sumie Yoshioka, Yukio Aso
Jan 18, 2003·Journal of Pharmaceutical Sciences·Duane T BrandauC Russell Middaugh
May 10, 2008·Biochimica Et Biophysica Acta·Vanessa CabraRoberto Arreguin-Espinosa
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Apr 10, 2013·Pharmaceutical Research·Nishant Kumar JainIpsita Roy
Feb 3, 2021·Carbohydrate Research·Prapti Behera, Seetharaman Balaji
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Aug 20, 2008·Molecular Pharmaceutics·Wenlei Jiang, Steven P Schwendeman
Jun 28, 2021·International Journal of Pharmaceutics·Hairui ZhangHugh D C Smyth

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