The Use of Chitosan to Enhance Photodynamic Inactivation against Candida albicans and Its Drug-Resistant Clinical Isolates

Abstract

Drug-resistant Candida infection is a major health concern among immunocompromised patients. Antimicrobial photodynamic inactivation (PDI) was introduced as an alternative treatment for local infections. Although Candida (C.) has demonstrated susceptibility to PDI, high doses of photosensitizer (PS) and light energy are required, which may be harmful to eukaryotic human cells. This study explores the capacity of chitosan, a polycationic biopolymer, to increase the efficacy of PDI against C. albicans, as well as fluconazole-resistant clinical isolates in planktonic or biofilm states. Chitosan was shown to effectively augment the effect of PDI mediated by toluidine blue O (TBO) against C. albicans that were incubated with chitosan for 30 min following PDI. Chitosan at concentrations as low as 0.25% eradicated C. albicans; however, without PDI treatment, chitosan alone did not demonstrate significant antimicrobial activity within the 30 min of incubation. These results suggest that chitosan only augmented the fungicidal effect after the cells had been damaged by PDI. Increasing the dosage of chitosan or prolonging the incubation time allowed a reduction in the PDI condition required to completely eradicate C. albicans. These results clearly indicate that combining chitosan with PDI is a promising antimicrobial approach to treat infectious diseases.

Assessment of Photodynamic Inactivation against Periodontal Bacteria Mediated by a Chitosan Hydrogel in a 3D Gingival Model

“…The complete eradication was achieved when a higher total light dose irradiation (>54 J·cm −2 ) was applied; namely, S. aureus biofilm can be completely eradicated by illuminating either 16 or 27 J·cm −2 of light dose per side with 2 h post-incubation. These results correlate with our previous findings that the augmented PDI efficacy relates to the post-incubation time of chitosan hydrogel and the damage level induced by PDI [23,28,29]. …”

“…Moreover, the minimum concentration of chitosan might vary, depending on the damage level induced by PDI and bacterial strains used. Meanwhile, we also found that chitosan alone could maximally induce 1-log reduction in planktonic cells without PDI, depending on the microbial strains used [23,28]. In this regard, it is possible that the chitosan hydrogel developed in this study might have some bactericidal effect without PDI.…”

“…However, as shown in Figure 4, with a total light dose of 108 J·cm −2 under four-sides illumination, a complete cell-killing could be found with 2 h post-incubation time (Figure 4B) but not with that of 0.5 h (Figure 4A). As mentioned above, the augmented PDI cytotoxicity relates to the chitosan concentration and its post incubation time [23,28]. In this regard, the difference between Figure 3B and Figure 4A with 27 J·cm −2 per side at the illumination site suggests that 0.5 h post-incubation time might not be enough to ensure the complete cell-killing with chitosan hydrogel.…”

“…Chitosan is a polycationic biopolymer, consisting of N -acetyl- d -glucosamine and β-1,4-linked d -glucosamine [21]. It has received a great deal of attention for medical and pharmaceutical applications owing to its excellent biocompatibility, negligible immunogenicity, and low cytotoxicity [22,23,24]. Additionally, numerous studies have reported its antimicrobial activity, which make it an attractive biopolymer for the development of drug delivery systems in treating infectious diseases [25,26,27].…”

Photoinactivation of Candida albicans using methylene blue as photosensitizer

“…The photosensitizer and light application specifically on the site affected by candidiasis, dramatically reduces the local and systemic side effects, allowing the photodynamic therapy to be seen as a promising treatment against Candida albicans 21 .…”