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Ultrashort Self-Assembling Peptide Hydrogel for the Treatment of Fungal Infections

1
Biofunctional Nanomaterials Group, School of Pharmacy, Queen’s University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL Belfast, Northern Ireland
2
Biology Department, Faculty of Science, Basra University, Basra, Iraq
*
Author to whom correspondence should be addressed.
Received: 4 May 2018 / Revised: 17 May 2018 / Accepted: 18 May 2018 / Published: 22 May 2018
(This article belongs to the Special Issue Gels from the Self-Assembling of Peptide-Based Compounds)
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Abstract

The threat of antimicrobial resistance to society is compounded by a relative lack of new clinically effective licensed therapies reaching patients over the past three decades. This has been particularly problematic within antifungal drug development, leading to a rise in fungal infection rates and associated mortality. This paper highlights the potential of an ultrashort peptide, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), encompassing hydrogel-forming and antifungal properties within a single peptide motif, thus overcoming formulation (e.g., solubility, drug loading) issues associated with many currently employed highly hydrophobic antifungals. A range of fungal susceptibility (colony counts) and cell cytotoxicity (MTS cell viability, LIVE/DEAD staining® with fluorescent microscopy, haemolysis) assays were employed. Scanning electron microscopy confirmed the nanofibrous architecture of our self-assembling peptide, existing as a hydrogel at concentrations of 1% w/v and above. Broad-spectrum activity was demonstrated against a range of fungi clinically relevant to infection (Aspergillus niger, Candida glabrata, Candida albicans, Candida parapsilosis and Candida dubliniensis) with greater than 4 log10 CFU/mL reduction at concentrations of 0.5% w/v and above. We hypothesise antifungal activity is due to targeting of anionic components present within fungal cell membranes resulting in membrane disruption and cell lysis. NapFFKK-OH demonstrated reduced toxicity against mammalian cells (NCTC 929, ARPE-19) suggesting increased selectivity for fungal cells. However, further studies relating to safety for systemic administration is required, given the challenges toxicity has presented in the wider context of antimicrobial peptide drug development. Overall this study highlights the promise of NapFFKK-OH hydrogels, particularly as a topical formulation for the treatment of fungal infections relating to the skin and eyes, or as a hydrogel coating for the prevention of biomaterial related infection. View Full-Text
Keywords: peptide; self-assembly; nanomaterial; hydrogel; aspergillosis; candidiasis peptide; self-assembly; nanomaterial; hydrogel; aspergillosis; candidiasis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Albadr, A.A.; Coulter, S.M.; Porter, S.L.; Thakur, R.R.S.; Laverty, G. Ultrashort Self-Assembling Peptide Hydrogel for the Treatment of Fungal Infections. Gels 2018, 4, 48.

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