TECHNOLOGYHistatin-5-Based Antifungal Peptides for Oral Topical Applications
Overview
Candida albicans is a fungus colonizing human mucosal surface. It commonly causes recurrent infections which can become life-threatening in immunosuppressed and immunocompromised patients. Histatin-5 (Hst-5) is a cationic antimicrobial peptide found in saliva with antifungal activity against C. albicans, related fungal organisms, and several bacteria. In a murine model of oral Candida infection, Hst-5 protected against infection of C. albicans in oral mucosa. Hst-5 has also been shown to clear existing lesions in the oral cavity and relieve associated tissue inflammation. The mechanism of action underlying its effect in Candida infections is different from the current standard of care of azole and polyene drugs and does not induce resistance. One limitation of the therapeutic potential of Hst-5 is that C. albicans is able to degrade and deactivate Hst-5 via a secreted proteolytic enzyme. This technology refers to Hst-5-derived antifungal peptides resistant to proteolysis and efficacious in treating or preventing Candida infections, and to their oral topical administration using a biocompatible hydrogel delivery system.
UMB researchers have developed a biocompatible hydrogel delivery system that is optimized for viscosity, stability, and controlled sustained release of Hst-5 and its derivatives. Efficacy of the hydrogel in inhibiting Candida adherence and biofilm formation on denture acrylic discs has been shown in vitro and in an ex vivo model of infection. As denture stomatitis is the most common Candida infection, an animal model of denture stomatitis has been to evaluate the efficacy of the formulation against biofilm formation on denture acrylic and infection of denture associated palatal tissue. Specifically, a denture appliance has been designed to fit the oral cavity of the rat model. Findings have demonstrated the suitability of the gel for use on denture acrylic material and in protecting palatal tissue against Candida infection. Findings from in vivo evaluation of the formulation in a mouse model of oral candidiasis demonstrated anti-inflammatory and tissue regeneration properties for the gel.
Applications
Oral candidiasis is common in infants, the elderly, cancer and diabetes patients, hospitalized patients, and is the most common opportunistic infection in HIV+ individuals. It can also lead to denture stomatitis in 70% of denture wearers, where an oral topical application of an antifungal can be a preventative strategy against infection. Candida colonizes other mucosal surfaces and the application of Hst-5 peptides via hydrogel is not limited to the oral cavity but other mucosal tissue as well. Approximately 30% of the estimated 46,000 healthcare-associated Candida infections among hospitalized patients in the US each year result in death. Each case of Candida infection results in 3–13 days of additional hospitalization and a total of $6,000–$29,000 in direct healthcare costs. Given the public health threat of these infections and their resistance to first and second line treatments, the global market for human antifungal therapeutics reached $11.8 billion in 2013 and is expected to grow to nearly $13.9 billion in 2018.
Advantages
Novel oral topical administration
Stage of Development
Hst-5 hydrogel has been tested in animal model of Candida infection; various Hst-5-derived peptides are at different stages of testing (in vitro, ex vivo and in vivo assays).
(RB- 10/17/17)
Licensing Potential
Available for licensing
Contact Info
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Phone: (410) 706-2380
