Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections.

Candida albicans can cause various types of oral infections, mainly associated with denture stomatitis. Conventional therapy has been linked to high recurrence, toxicity, and fungal resistance, necessitating the search for new drugs and delivery systems. In this study, caffeic acid phenethyl ester (CAPE) and gellan gum (GG) were studied as an antifungal agent and carrier system, respectively. First, we observed that different GG formulations (0.6 to 1.0% wt/vol) were able to incorporate and release CAPE, reaching a controlled and prolonged release over 180 min at 1.0% of GG. CAPE-GG formulations exhibited antifungal activity at CAPE concentrations ranging from 128 to >512 µg/mL. Furthermore, CAPE-GG formulations significantly decreased the fungal viability of C. albicans biofilms at short times (12 h), mainly at 1.0% of GG (p < 0.001). C. albicans protease activity was also reduced after 12 h of treatment with CAPE-GG formulations (p < 0.001). Importantly, CAPE was not cytotoxic to human keratinocytes, and CAPE-GG formulations at 1.0% decreased the fungal burden (p = 0.0087) and suppressed inflammation in a rat model of denture stomatitis. Altogether, these results indicate that GG is a promising delivery system for CAPE, showing effective activity against C. albicans and potential to be used in the treatment of denture stomatitis.

Metal Nanoparticles to Combat Candida albicans Infections: An Update.

Candidiasis is an opportunistic mycosis with high annual incidence worldwide. In these infections, Candida albicans is the chief pathogen owing to its multiple virulence factors. C. albicans infections are usually treated with azoles, polyenes and echinocandins. However, these antifungals may have limitations regarding toxicity, relapse of infections, high cost, and emergence of antifungal resistance. Thus, the development of nanocarrier systems, such as metal nanoparticles, has been widely investigated. Metal nanoparticles are particulate dispersions or solid particles 10-100 nm in size, with unique physical and chemical properties that make them useful in biomedical applications. In this review, we focus on the activity of silver, gold, and iron nanoparticles against C. albicans. We discuss the use of metal nanoparticles as delivery vehicles for antifungal drugs or natural compounds to increase their biocompatibility and effectiveness. Promisingly, most of these nanoparticles exhibit potential antifungal activity through multi-target mechanisms in C. albicans cells and biofilms, which can minimize the emergence of antifungal resistance. The cytotoxicity of metal nanoparticles is a concern, and adjustments in synthesis approaches or coating techniques have been addressed to overcome these limitations, with great emphasis on green synthesis.

The biocompatibility and antifungal effect of Rosmarinus officinalis against Candida albicans in Galleria mellonella model.

This study was performed to evaluate the biocompatibility and antifungal effect of Rosmarinus officinalis against Candida albicans in Galleria mellonella model. Five different concentrations of R. officinalis glycolic extract (50; 25; 12.5 e 6.25 mg/mL) were used to evaluate its biocompatibility in G. mellonella model, in which the nystatin suspension (100; 50; 25; 12.5 e 6.25%) was used as a control group. The antifungal action of R. officinalis glycolic extract was evaluated on C. albicans for 72, 48 and 12 h at two different phases: (1) using the extract as therapeutic agent; and (2) using the extract as prophylactic agent. PBS was used as a negative control group. G. mellonella survival curves were plotted using the Kaplan-Meier method and statistical analysis was performed using the log-rank test (Mantel-Cox) and the significance level was set at (α ≤ 0.05). There was no significant difference among the groups in which all were biocompatible except of a significant death rate of 26.6% with nystatin 100%. In phase 1, it was found that after 7 days, there was no statistically significant difference among the prophylactic treatment groups. In phase 2, the groups of R. officinalis 6.25 mg/mL for 72 h and R. officinalis of 12.5 mg/mL for 24 h promoted the survival rate of the larvae in comparison with the control group with a significant difference (p = 0.017) and (p = 0.032) respectively. Therefore, R. officinalis extract is biocompatible in different concentrations and can be used as a prophylactic agent against fungal infection.

Farnesol as a potentiator of antimicrobial photodynamic inactivation on Enterococcus faecalis.

Enterococcus faecalis is related to the recurrence of endodontic infections and approaches to intracanal disinfection are necessary. Farnesol, an alcohol commonly found in propolis, has antimicrobial properties, and can enhance the efficacy of some antibiotic therapies. The objective was to evaluate whether farnesol can increase the efficacy of the antimicrobial photodynamic inactivation (aPDI) on E. faecalis, investigating its action on planktonic growth, biofilms, and cell permeability. Planktonic cells and biofilms of E. faecalis were pre-treated with farnesol (0.25 mM) 2 h before aPDI. Methylene blue (1 mg/mL) and laser (660 nm) were employed in the aPDI. As a result, farnesol was able to increase the antimicrobial activity of aPDI in both planktonic and biofilm stages, reaching cell reductions of 4.6 to 6 log10 CFU and 1.3 to 3 log10 CFU, respectively, when compared to aPDI isolated. The efficacy of farnesol in enhancing the anti-biofilm activity of aPDI was also confirmed by electron microscopy, in which a smaller number of bacterial cells and extracellular matrix were verified in the combined therapy compared to aPDI alone. The potentiating action of farnesol was associated with its effects in increasing the cell permeability and methylene blue uptake by the bacterial cells. Therefore, farnesol can be a promising potentiator of aPDI against E. faecalis.

Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis.

Candidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.

Oral Colonization by Candida Species in Patients with Multiple Sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease that affects the central nervous system. Since immune system plays a key role in this disease, patients with MS can present higher risk of infections. PURPOSE: This study aimed to investigate the prevalence of Candida spp. in the oral cavity of MS patients in relation to a control group METHODS: In total, 100 individuals were selected: 55 diagnosed with MS and 45 healthy individuals (control group). Saliva samples were collected and seeded in culture media selecting for Candida. Following an incubation period of 48 h, colony-forming units (CFU mL-1) were counted and colonies were isolated for Candida species identification by multiplex PCR. The results were analysed by chi-squared and Mann-Whitney U statistical tests considering a significance level of 5%. RESULTS: Candida spp. were confirmed in the oral cavity of 50.09% patients in the MS group and 35.55% individuals in the control group. In individuals positive for the growth of Candida spp., the median values of Candida colonies were 220 CFU mL-1 for the MS group and 120 CFU mL-1 for the control group. However, no statistically significant differences were observed between groups for both prevalence and CFU mL-1 count. Of the Candida species identified, 73.91% were C. albicans, 21.73% C. glabrata, 2.17% C. tropicalis, and 2.17% C. krusei. CONCLUSIONS: The colonization of Candida spp. in the oral cavity of individuals with multiple sclerosis was higher than in the control group; however these findings were not proven to be statistically significant.

Antimicrobial photodynamic therapy against clinical isolates of carbapenem-susceptible and carbapenem-resistant Acinetobacter baumannii.

Infections caused by Acinetobacter baumannii have become a challenge for healthcare professionals because of the rapid increase in Gram-negative bacteria resistant to carbapenem antibiotics. The objective of this study was to evaluate the effect of antimicrobial photodynamic therapy (aPDT) against different strains of A. baumannii isolated from patients with infectious process and hospitalized at the intensive care unit of the hospitals of São Jose dos Campos, São Paulo. These isolates were obtained from the Valeclin Clinical Analysis Laboratory (SP, Brazil) and were tested for susceptibility to the carbapenems imipenem and meropenem by determination of the minimal inhibitory concentration (MIC) using the broth microdilution method. The strains susceptible and resistant to these antibiotics were submitted to aPDT using methylene blue and a low-level laser with a wavelength of 660 nm and fluence of 39.5 J/cm2 (energy of 15 J and time of 428 s). The number of colony-forming units (CFU/mL) was analyzed by ANOVA and the Tukey test. The laboratory of origin of the clinical isolates identified 1.54% of 13,715 strains tested over a period of 8 months as A. baumannii. Among the A. baumannii isolates, 58% were resistant to carbapenems by the disk diffusion test. Susceptible isolates exhibited MIC of 0.5 to 1 µg/mL and resistant isolates of 64 to > 128 µg/mL. PDT reduced the number of A. baumannii cells for all isolates tested, with this reduction ranging from 63 to 88% for susceptible isolates and from 26 to 97% for resistant isolates. The percentage of viability was dependent on the strain analyzed. In conclusion, these data indicate that PDT could be an alternative strategy for the control of infections caused by carbapenem-resistant A. baumannii.