Can a New Drug Formulation Treat Candida Infections

Candida albicans infections in the mouth are often painful for people who develop infections such as burning mouth syndrome or thrush. To provide effective treatment, scientists at the University of Bristol in the United Kingdom have developed a new drug formulation to improve the efficiency of currently approved antifungal drugs used to treat Candida infections, while also lessening the drug’s side effects. 

The antibiotic, fluconazole, has been approved to treat Candida infections, however, the drug is ineffective in treating Candida biofilms. People with C. albicans infections in the oral cavity may experience thrush, oral stomatitis, or burning mouth syndrome, while others with compromised immune systems can face life-threatening bloodstream infections (candidemia) with drug-resistant Candida. Scientists worldwide continue to combat the growing problem of antimicrobial resistance (AMR).

In an effort to improve the activity of fluconazole against these infections, researchers used a chemical signaling molecule secreted by another bacterial pathogen, Pseudomonas aeruginosa, to enhance the activity of one of the most common antifungal drugs, fluconazole. 

The study, “A Novel, Quorum Sensor-Infused Liposomal Drug Delivery System Suppresses Candida Albicans Biofilms,” published in International Journal of Pharmaceutics, found that “packaging the bacterial signaling molecule and fluconazole into microscopic lipid molecules and delivering them to Candida biofilms significantly increases the efficacy of fluconazole. Bacterial signaling molecules are naturally existing and cost-effective to mass produce. Therefore, the novel drug formulation, with further optimizations, will be a promising and cost-effective treatment option for both oral and non-oral Candida infections,” explains Nihal Bandara,BDS (HONS), PhD (HK), corresponding author and lecturer in oral microbiology in the Bristol Dental School at the University of Bristol.

 Microbes use chemical signals (quorum sensing molecules) to communicate with the same species, different species, or different kingdoms. According to past studies, findings indicate these signal molecules can increase/decrease the efficiency of antimicrobial drugs by increasing/decreasing the sensitivity of the microorganisms to the particular agent. 

“Microbials chemical signals play a crucial role in the formation, maintenance, and the spread of the biofilms, therefore the causation and the progress of various infections. The control or manipulation of these signals allows us to manage infections effectively,” Bandara says. 

Using four formulations of liposomes with fluconazole, researchers found co-delivering fluconazole with a Pseudomonas aeruginosa quorum sensing molecule, N-3-oxo-dodecanoyl-L-homoserine lactone (C12AHL), in a liposomal formulation suppressed C. albicans biofilms.

“The efficacy of fluconazole increases more evidently when the bacterial signal molecule and antifungal drug are delivered in the form of lipid formulation. The direct administration of the two agents did not produce Candida inhibitory effects with similar magnitude,” explains Bandara. “In fact, the signaling molecule at lower doses may revert its action if administered as a free agent [revealed by a follow-up study]. Therefore, the effect we observed is specific and formulation dependent.”

The new formulation may result in the development of topical applications, oral rinses, and denture cleansers to effectively treat and control C. albicans infections. 

The study was funded by the Innovation in Oral Care Award received by Bandara from the International Association for Dental Research (IADR), partnering with GlaxoSmithKline.