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Pre-formulation and delivery strategies for the development of bacteriocins as next generation antibiotics
Date
2021
Abstract
Bacteriocins, a class of antimicrobial peptide produced by bacteria, may offer a potential alternative to traditional antibiotics, an important step towards mitigating the ever-increasing antimicrobial resistance crisis. They are active against a range of clinically relevant Gram-positive and Gram-negative bacteria. Bacteriocins have been discussed in the literature for over a century. Although they are used as preservatives in food, no medicine based on their antimicrobial activity exists on the market today. In order to formulate them into clinical antibiotics, pre-formulation studies on their biophysical and physicochemical properties that will influence their activity in vivo and their stability during manufacture must be elucidated. Thermal, pH and enzymatic stability of bacteriocins are commonly studied and regularly reported in the literature. Solubility, permeability and aggregation properties on the other hand are less frequently reported for many bacteriocins, which may contribute to their poor clinical progression. Promising cytotoxicity studies report that bacteriocins exhibit few cytotoxic effects on a variety of mammalian cell lines, at active concentrations. This review highlights the lack of quantitative data and in many cases even qualitative data, on bacteriocins’ solubility, stability, aggregation, permeability and cytotoxicity. The formulation strategies that have been explored to date, proposed routes of administration, trends in in vitro/in vivo behaviour and efforts in clinical development are discussed. The future promise of bacteriocins as a new generation of antibiotics may require tailored local delivery strategies to fulfil their potential as a force to combat antimicrobial-resistant bacterial infections.
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Description
Publisher
Elsevier
Citation
European Journal of Pharmaceutics and Biopharmaceutics, 2021, 165, pp. 149-163
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Funding Information
This work was supported by the Science Foundation of Ireland (Grant 13/CDA/2122), SSPC, the SFI Research Centre for Pharmaceuticals (Grant 12/RC/2275_p2), the Irish Research Council (Grant GOIPG/2018/3041) and the Department of Chemical Sciences, University of Limerick, Ireland. Graphical abstract created with BioRender.com
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Type
Article
Rights
https://creativecommons.org/licenses/by-nc-sa/4.0/