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Antimicrob Agents Chemother. 2015 Nov 23;60(2):881-9. doi: 10.1128/AAC.02624-15. Print 2016 Feb.

Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis.

Author information

1
Department of Molecular Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland, USA.
2
Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland, USA.
3
School of Pharmacy, University of Maryland, Baltimore, Maryland, USA.
4
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, USA.
5
Department of Molecular Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland, USA mrizk@umaryland.edu.

Abstract

Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV(+) individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent.

PMID:
26596951
PMCID:
PMC4750700
DOI:
10.1128/AAC.02624-15
[Indexed for MEDLINE]
Free PMC Article

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