Considering the challenges related to antimicrobial resistance, other strategies for controlling infections have been suggested, such as antimicrobial photodynamic therapy (aPDT) and antimicrobial peptides (AMP). This study aims to perform a systematic review and meta-analysis to obtain evidence on the antimicrobial effectiveness of aPDT associated with AMP and establish in vitro knowledge on this topic for further study designs. The PubMed, Scopus, Web of Science, Science Direct, Scielo, and Cochrane Library databases were searched. Two independent and calibrated researchers (Kappa = 0.88) performed all the systematic steps according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The odds ratio (OR) was used as the effect measure. The Peto method was used to perform the meta-analysis due to the sparse data. Twenty studies were included in the present review. The result was significant (OR = 0.14/p = 0.0235/I-squared = 0%), showing better outcomes of aPDT associated with peptides than those of aPDT alone for controlling the microbial load. Only 20% of the studies included evaluated this approach in a biofilm culture. Combined treatment with aPDT and AMP highly increased the ability of microbial reduction of Gram-positive and Gram-negative bacteria. However, additional blind studies are required to evaluate the efficacy of this therapy on microbial biofilms.

This study aimed to evaluate the potential of successive applications of sub-lethal doses of the antimicrobial photodynamic therapy (aPDT) mediated by Photodithazine^® (PDZ) and curcumin (CUR) associated with LED in the viability, reactive oxygen species (ROS) production, and gene expression of Candida albicans. The microbial assays were performed using planktonic cultures and biofilms. Ten successive applications (Apl#) were performed: aPDT (P+L+; C+L+), photosensitizer (P+L−; C+L−), and LED (P−L+; C−L+). Control groups were used (P−L−; C−L−). The viability of C. albicans was determined by cultivating treated cultures on agar plates with or without fluconazole (FLU). In addition, the ROS detection and expression of SOD1, CAP1, and ERG11 genes were determined. For planktonic cultures, no viable colonies were observed after Apl#3 (without FLU) and Apl#2 (with FLU) for either photosensitizer. Biofilm treated with P+L+ resulted in the absence of cell viability after Apl#7, while C+L+ showed ~1.40 log₁₀ increase in cell viability after Apl#2, regardless of FLU. For both photosensitizers, after the last application with viable colonies, the production of ROS was higher in the biofilms than in the planktonic cultures, and SOD1 expression was the highest in P+L+. A reduction of CAP1 and ERG11 expression occurred after P+L+, regardless of FLU. C+L+ had a higher level of ROS, and the treatments were non-significant for gene expression. Sub-lethal doses of aPDT mediated by CUR could induce C. albicans resistance in biofilms, while C. albicans cells in biofilms were susceptible to aPDT mediated by PDZ.

Antimicrobial photodynamic therapy (aPDT) is a method that does not seem to promote antimicrobial resistance. Photosensitizers (PS) conjugated with inorganic nanoparticles for the drug-delivery system have the purpose of enhancing the efficacy of aPDT. The present study was to perform a systematic review and meta-analysis of the efficacy of aPDT mediated by PS conjugated with inorganic nanoparticles. The PubMed, Scopus, Web of Science, Science Direct, Cochrane Library, SciELO, and Lilacs databases were searched. OHAT Rob toll was used to assess the risk of bias. A random effect model with an odds ratio (OR) and effect measure was used. Fourteen articles were able to be included in the present review. The most frequent microorganisms evaluated were Staphylococcus aureus and Escherichia coli, and metallic and silica nanoparticles were the most common drug-delivery systems associated with PS. Articles showed biases related to blinding. Significant results were found in aPDT mediated by PS conjugated with inorganic nanoparticles for overall reduction of microorganism cultured in suspension (OR = 0.19 [0.07; 0.67]/p-value = 0.0019), E. coli (OR = 0.08 [0.01; 0.52]/p-value = 0.0081), and for Gram-negative bacteria (OR = 0.12 [0.02; 0.56/p-value = 0.0071). This association approach significantly improved the efficacy in the reduction of microbial cells. However, additional blinding studies evaluating the efficacy of this therapy over microorganisms cultured in biofilm are required.

The efficacy of Zerumbone (ZER) against mixed biofilms of fluconazole-resistant Candida albicans (ATCC 96901) and Streptococcus mutans (UA159) was evaluated. Biofilms were cultivated on acrylic resin specimens for 48 h, with alternating supplementation of glucose and sucrose. ZER's ability to inhibit biofilm formation (pre-treatment) and eradicate mature biofilms (post-treatment) was assessed. Control groups were treated with Chlorhexidine (CHX), Nystatin (NYS), Penicillin (ATB), and distilled water. The efficacy was measured by colony forming units (CFU/mm²) counts, biomass and biofilm's matrix components quantification (water-soluble polysaccharides [WSP], alkali-soluble polysaccharides [ASPs], proteins, and extracellular DNA [eDNA]). Data were analyzed by one-way ANOVA with Tukey's or Gammes-Howell post-hoc test for normal data and Kruskal-Wallis test for data that did not meet the assumption of normality (α = 0,05). In the biofilm inhibition assay, ZER decreased total microbiota (C. albicans + S. mutans) (2.7 log₁₀; p < 0.005), C. albicans (1.4 log₁₀; p < 0.038) and S. mutans (1.9 log₁₀; p < 0.048) counting (vs control group), and biofilm components [insoluble proteins: 37% (p < 0.001); WSP: 13% (p < 0.042); ASP: 46% (p < 0.001); eDNA: 11% (p < 0.048)]. Post-treatment with ZER reduced total microbiota (3.2 log₁₀; p < 0.001), C. albicans (3 log₁₀; p < 0.001) and S. mutans (2 log₁₀; p < 0.001) counting (vs control group), and biofilm components [soluble proteins: 20% (p < 0.001); WSP: 20% (p < 0.001); ASP: 51% (p < 0.001); and eDNA: 33% (p < 0.001)]. The positive control groups demonstrated similar or lower efficacy than ZER under all experimental conditions. ZER demonstrates efficacy against mixed biofilms by reducing C. albicans and S. mutans counting and disrupting the extracellular matrix in both assays.

The aim of the study was to investigate the effect of antimicrobial peptides (AMPs) Hylin−a1, KR−12-a5, and Temporin-SHa in Candida albicans as well as the biocompatibility of keratinocytes spontaneously immortalized (NOK-si) and human gingival fibroblasts (FGH) cells. Initially, the susceptible (CaS—ATCC 90028) and fluconazole-resistant (CaR—ATCC 96901) C. albicans strains were grown to evaluate the effect of each AMP in planktonic culture, biofilm, and biocompatibility on oral cells. Among the AMPs evaluated, temporin−SHa showed the most promising results. After 24 h of Temporin-SHa exposure, the survival curve results showed that CaS and CaR suspensions reduced 72% and 70% of cell viability compared to the control group. The minimum inhibitory/fungicide concentrations (MIC and MFC) showed that Temporin−SHa was able to reduce ≥50% at ≥256 µg/mL for both strains. The inhibition of biofilm formation, efficacy against biofilm formation, and total biomass assays were performed until 48 h of biofilm maturation, and Temporin-SHa was able to reduce ≥50% of CaS and CaR growth. Furthermore, Temporin−SHa (512 µg/mL) was classified as non-cytotoxic and slightly cytotoxic for NOK-si and FGH, respectively. Temporin−SHa demonstrated an anti-biofilm effect against CaS and CaR and was biocompatible with NOK-si and FGH oral cells in monolayer.