Abstract
Stabilisation of protein/peptide drugs against thermal denaturation is a challenging problem, especially for liquid formulations. Various polysaccharides at high concentrations have been reported to improve stability of polypeptides, probably by providing a crowded environment which retards kinetic unfolding and resultant degradation. Levan is a fructose homopolysaccharide which is finding increasing use in pharmaceutical applications, but its use for protein drug stabilization remains meagre. In this study, we used levan for stabilizing a liquid preparation of a peptide antibiotic, bacitracin. We prepared liquid formulations of bacitracin with or without levan and subjected them to storage at 25 °C. The stored samples were then analysed over 120 days for denaturation and antibacterial activity. Differential Scanning Calorimetry, Circular Dichroism and High Performance Liquid Chromatography were used for evaluating the effect of levan on thermal denaturation of bacitracin. We found that levan at 2.5% w/v significantly preserved the antibacterial activity of bacitracin for 120 days as compared to plain buffered bacitracin, even when stored at 25 °C. Also, levan at high concentrations maintained the secondary structure and increased the melting temperature (Tm) of bacitracin in solution. Levan did not form covalent interactions or strong complexation with bacitracin. Based on this study, levan appears as a promising stabilizing agent for preparing liquid formulations of protein/peptide drugs that can be stored at room temperature.
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Acknowledgements
The authors are grateful to thank the Department of Science and Technology (DST) sponsored National Facility for Drug Development (NFDD) and Defence Research Development Organisation, Government of India for their constant support. They also thank Defense Research Development Organisation, New Delhi for the sponsored project entitled "Stabilisation of Plague (A potential bioweapon) Vaccine using Biocompatible Polysaccharides"
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Soja Sreenivasan and Ruckmani Kandasamy declare that this article content has no conflicts of interest.
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Sreenivasan, S., Kandasamy, R. Levan: A Biocompatible Homopolysaccharide Excipient for Stabilization of Peptide Drugs. Int J Pept Res Ther 23, 305–311 (2017). https://doi.org/10.1007/s10989-016-9562-4
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DOI: https://doi.org/10.1007/s10989-016-9562-4