Targeted photodynamic therapy of fungal infections using rose bengal and nanoparticles

Abstract

Photodynamic therapy (PDT) is a successful treatment of specific oncological and infectious diseases; it also emerges to be effective in the treatment of onychomycosis, a fungal infection of the nail often caused by commonly clinically-relevant dermatophytes: Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton interdigitale. Rose bengal (RB) solutions combined with a green laser have proven to be efficient in clearing nail infections caused by T. rubrum in a human pilot study and in extensive in vitro experiments. The antifungal activity of PDT against the last two dermatophytes has yet to be studied. PDT relies on a drug, called photosensitizer (PS) that absorbs light at a selected wavelength. The associated photochemical process damages abnormal cells by producing reactive oxygen species (ROS). Among the various PSs used to treat fungal infections, RB takes a special place because of its cytotoxicity when laser-activated. However, there is a potential problem associated with RB application in patients: RB has limited penetration through the nail due to dilution or dispersion over the tissue, which may compromise its ability to kill fungus spores. Nanoparticles carrying RB can alleviate the problem of dilution and are reported to effectively penetrate through the nail. Chitosan nanoparticles demonstrated antifungal activity and are effective in penetrating tissue barriers, for this reason, they can function as carriers for RB delivery through the nail. This thesis aims: 1. To test the antifungal activity of RB coupled with a green laser against three common dermatophytes. 2. To fabricate, purify and characterise monodisperse chitosan nanoparticles for biomedical application. To devise a simple protocol for synthesising RB-encapsulated chitosan nanoparticles and characterise their size, morphology and chemical structure. 4. To test the PDT efficiency of chitosan nanoparticles carrying RB against three clinically-relevant pathogens in vitro and confirm their biological safety. The findings suggest that RB-PDT and PDT in combination with RB-nanoparticles can act against a broader spectrum of fungal pathogens.With continued development they may also be employed in a wider range of clinical antifungal applications. Future work related to assessing the PDT efficiency of nanoparticles on in vivo animal models following pre-clinical and clinical studies targeting antifungal drug treatment of onychomycosis is recommended.

Date of Award	2022
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Antonio Lauto (Supervisor)