Herbal-loaded drug delivery nanotechnological systems have been extensively studied recently. The antimicrobial activity of medicinal plants has shown better pharmacological action when such plants are loaded into a drug delivery system than when they are not loaded. Syngonanthus nitens Bong. (Rhul.) belongs to the Eriocaulaceae family and presents antiulcerogenic, antioxidant, antibacterial, and antifungal activity. The aim of this study was to evaluate the antifungal activity of Syngonanthus nitens (S. nitens) extract that was not loaded (E) or loaded (SE) into a liquid crystal precursor system (S) for the treatment of vulvovaginal candidiasis (VVC) with Candida albicans. The minimal inhibitory concentration (MIC) was determined by the microdilution technique. Additionally, we performed hyphae inhibition and biofilm tests. Finally, experimental candidiasis was evaluated in in vivo models with Wistar female rats. The results showed effective antifungal activity after incorporation into S for all strains tested, with MICs ranging from 31.2 to 62.5 μg/mL. Microscopic observation of SE revealed an absence of filamentous cells 24 h of exposure to a concentration of 31.2 μg/mL. E demonstrated no effective action against biofilms, though SE showed inhibition against biofilms of all strains. In the in vivo experiment, SE was effective in the treatment of infection after only two days of treatment and was more effective than E and amphotericin B. The S. nitens is active against Candida albicans (C. albicans) and the antifungal potential is being enhanced after incorporation into liquid crystal precursor systems (LCPS). These findings represent a promising application of SE in the treatment of VVC.

We have previously reported on the activity of different extracts from Astronium sp. against Candida albicans, with the hydroethanolic extract prepared from leaves of A. urundeuva, an arboreal species widely distributed in arid environments of South America and often used in folk medicine, displaying the highest in vitro activity. Here we have further evaluated the antifungal activity of this extract against strains of C. albicans and C. glabrata, the two most common etiological agents of candidiasis. The extract was tested alone and loaded into a nanostructured lipid system (10% oil phase, 10% surfactant and 80% aqueous phase, 0.5% Poloxamer 407^®). In vitro susceptibility assays demonstrated the antifungal activity of the free extract and the microemulsion against both Candida species, with increased activity against C. glabrata, including collection strains and clinical isolates displaying different levels of resistance against the most common clinically used antifungal drugs. Checkerboard results showed synergism when the free extract was combined with amphotericin B against C. albicans. Serial passage experiments confirmed development of resistance to fluconazole but not to the free extract upon prolonged exposure. Although preformed biofilms were intrinsically resistant to treatment with the extract, it was able to inhibit biofilm formation by C. albicans at concentrations comparable to those inhibiting planktonic growth. Cytotoxicity assays in different cell lines as well as an alternative model using Artemia salina L. confirmed a good safety profile of the both free and loaded extracts, and an in vivo assay demonstrated the efficacy of the free and loaded extracts when used topically in a rat model of vaginal candidiasis. Overall, these results reveal the promise of the A. urundeuva leaves extract to be further investigated and developed as an antifungal.

Throughout the genetic and physiological evolution of microorganisms, the microbiological sciences have been expanding the introduction of new therapeutic trials against microbial diseases. Special attention has been paid to the bacterium Helicobacter pylori, which induces gastric infections capable of causing damage, ranging from acute and chronic gastritis to the development of gastric cancer and death. The use of compounds with natural origins has gained popularity in scientific research focused on drug innovation against H. pylori because of their broad flexibility and low toxicity. The aim of this study was to describe the use of natural products against H. pylori in order to clarify important parameters for related fields. The study demonstrated the vast therapeutic possibilities for compounds originating from natural sources and revealed the need for innovations from future investigations to expand the therapeutic arsenal in the fight against H. pylori infection.

The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX₂(INH)₂]·nH₂O (X = Cl⁻ and n = 1 (1); X = NCS⁻ and n = 5 (2); X = NCO⁻ and n = 4 (3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS⁻ or NCO⁻) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2′,2′′,2′′′-(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij^® 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC^® 25923 and Escherichia coli ATCC^® 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC₅₀) against the Vero cell line (ATCC^® CCL-81^TM) were used to calculate the selectivity index (SI). Among the free compounds, only compound 2 (MIC 500 μg/mL) showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC’s 125, 125 and 500 μg/mL, respectively) and S. aureus (MICs 250, 500 and 125 μg/mL, respectively). The loaded compounds were less toxic against the Vero cell line, especially compound 1 (IC₅₀ from 109.5 to 319.3 μg/mL). The compound 2- and 3-loaded MEs displayed the best SI for E. coli and S. aureus, respectively. These results indicated that the Cu(II) complex-loaded MEs were considerably more selective than the free compounds, in some cases, up to 40 times higher.

Candidiasis is one of the most frequent nosocomial infections affecting an increasing number of at-risk patients. Candida albicans remains the most frequent causative agent of candidiasis, but, in the last decade, C. auris has emerged as a formidable multi-drug-resistant pathogen. Both species are fully capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. Here, we have screened the Repurposing Hub library from the Broad Institute, containing over 6000 compounds, in search for inhibitors of C. albicans and C. auris biofilm formation. The primary screen identified 57 initial hits against C. albicans and 33 against C. auris. Confirmatory concentration-dependent assays were used to validate the activity of the initial hits and, at the same time, establish their anti-biofilm potency. Based on these results, ebselen, temsirolimus, and compound BAY 11-7082 emerged as the leading repositionable compounds. Subsequent experiments established their spectrum of antifungal activity against yeasts and filamentous fungi. In addition, their in vivo activity was examined in the murine models of hematogenously disseminated C. albicans and C. auris infections. Although promising, further in vitro and in vivo studies are needed to confirm their potential use for the therapy of candidiasis and possibly other fungal infections.