Triggered Anti-Fungal Hydrogels for the Treatment of Candida Infections
Abstract
Military wounds are highly susceptible to microbial infiltration, which can lead to systemic infections, causing significant patient"" morbidity and even increased mortality. Fungi are a major source of these infections, particularly Candida. Fungal resistance is on" the rise andtoxicity of typical antifungal therapeutics can lead to additional complications during treatment. Local anti-fungal drug release therapies that limit exposure to these therapeutics can mitigate both of these issues. The proposed work will focus on the development of a fungal enzyme responsive hydrogel material that can be applied locally to a variety of military infections ande"nable triggered-release of the encapsulated anti-fungal drugs, thereby controlling exposure. The hydrogel backbone will be formed of" a bioinert polymer conjugated to a library of peptides with varying Candida secreted aspartic protease (Saps) cleavage kinetics. Sap production is upregulated in virulent fungal strains and specific SAP gene profiles have been related todifferent strains of Candida along with planktonic versus biofilm fungi. We will formulate these materials and examine their drug release kinetics in the pre"sence of Candida Saps, focusing primarily on strains of C. albicans. We will work with ONR Global and Dr. Juliana Campos Junqueira,"" Associate Professor of Microbiology and Immunology at Univ Estadual Paulista/UNESP in S~o Jos~ dos Campos, Brazil, to study the in" vitro and in vivo effects of these hydrogel materials. The in vitro efficacy will be established against C. albicans biofilm strain"s. Following this, in vivo performance of the most effective hydrogel formulations will be investigated in both a rat oral candidias"is model as well as mouse burn wound candidiasis model. These animal studies will be performed by Dr. Junqueira at UNESP with approval of the UNESP Animal Ethics Committee using the materials developed and provided by Dr. Shukla at Brown University. Both the oral and burn wound infection models are highly relevant for military combat and non-combat related injuries along with civilian injuries. The technologies developed through this proposal will be applicable to both military and civilian applications.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 07, 2017
- Source ID
- N000141712651
Entities
People
- Anita Shukla
Organizations
- Brown University
- Office of Naval Research
- United States Navy