Highlights Regarding the Use of Metallic Nanoparticles against Pathogens Considered a Priority by the World Health Organization.

The indiscriminate use of antibiotics has facilitated the growing resistance of bacteria, and this has become a serious public health problem worldwide. Several microorganisms are still resistant to multiple antibiotics and are particularly dangerous in the hospital and nursing home environment, and to patients whose care requires devices, such as ventilators and intravenous catheters. A list of twelve pathogenic genera, which especially included bacteria that were not affected by different antibiotics, was released by the World Health Organization (WHO) in 2017, and the research and development of new antibiotics against these genera has been considered a priority. The nanotechnology is a tool that offers an effective platform for altering the physicalchemical properties of different materials, thereby enabling the development of several biomedical applications. Owing to their large surface area and high reactivity, metallic particles on the nanometric scale have remarkable physical, chemical, and biological properties. Nanoparticles with sizes between 1 and 100 nm have several applications, mainly as new antimicrobial agents for the control of microorganisms. In the present review, more than 200 reports of various metallic nanoparticles, especially those containing copper, gold, platinum, silver, titanium, and zinc were analyzed with regard to their anti-bacterial activity. However, of these 200 studies, only 42 reported about trials conducted against the resistant bacteria considered a priority by the WHO. All studies are in the initial stage, and none are in the clinical phase of research.

Improved in vitro and in vivo Anti-Candida albicans Activity of Cymbopogon nardus Essential Oil by Its Incorporation into a Microemulsion System.

PURPOSE: Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection that adversely affects a woman's health, due to unpleasant symptoms, therapeutic challenges, and the emergence of resistant strains. The association of natural products and nanotechnology is important to improve the antifungal potential of medicinal plants. We aimed to evaluate the in vitro and in vivo anti-Candida albicans activity of unloaded (EO) and loaded (ME+EO) essential oil of Cymbopogon nardus in the microemulsion (ME). METHODS: The chemical analysis of the EO was performed by gas chromatography-mass spectrometry. The ME and ME+EO were characterized by scattering, zeta potential, polarized light microscopy, rheological assays, mucoadhesiveness and transmission electronic microscopy. The in vitro antifungal activity of the EO and ME+EO were evaluated by microdilution technique. The toxicity of EO and ME+EO was analyzed on human cell line HaCat and using alternative model assay with Artemia salina. The experimental in vivo VVC was performed in female mice (C57BL/6). RESULTS: The main compounds of the EO were found to be citronellal, geranial, geraniol, citronellol, and neral. The formulations exhibited suitable size, homogeneity, negative charge, isotropic behavior, highly organized structure, and pseudoplastic behavior, for vaginal application. TEM photomicrographs showed possible EO droplets inside the spherical structures. The EO, when loaded into the ME, exhibited an improvement in its antifungal action against C. albicans. The EO was not toxic against brine shrimp nauplii. An in vivo VVC assay showed that the use of the ME significantly improved the action of the EO, since only the ME+EO promoted the eradication of the fungal vaginal infection on the third day of treatment. CONCLUSION: The EO and ME+EO are promising alternatives for the control of fungal infections caused by C. albicans, once the use of nanotechnology significantly improved the antifungal action of the EO, especially in an in vivo model of VVC.

Antifungal Activity of a Hydroethanolic Extract From Astronium urundeuva Leaves Against Candida albicans and Candida glabrata.

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.

Mucoadhesive In Situ Gelling Liquid Crystalline Precursor System to Improve the Vaginal Administration of Drugs.

The vaginal mucosa is a very promising route for drug administration due to its high permeability and the possibility to bypass first pass metabolism; however, current vaginal dosage forms present low retention times due to their dilution in vaginal fluids, which hampers the efficacy of many pharmacological treatments. In order to overcome these problems, this study proposes to develop a mucoadhesive in situ gelling liquid crystalline precursor system composed of 30% of oleic acid and cholesterol (7:1), 40% of ethoxylated and propoxylated cetyl alcohol, and 30% of a dispersion of 16% Poloxamer 407. The effect of the dilution with simulated vaginal fluid (SVF) on this system was evaluated by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological studies, texture profile analysis (TPA), mucoadhesion study, in vitro drug release test using hypericin (HYP) as drug model, and cytotoxicity assay. PLM and SAXS confirmed the formation of an isotropic system. After the addition of three different concentrations of SVF (30, 50, and 100%), the resultant formulations presented anisotropy and characteristics of viscous lamellar phases. Rheology shows that formulations with SVF behaved as a non-Newtonian fluid with suitable shear thinning for vaginal application. TPA and mucoadhesion assays indicated the formation of long-range ordered systems as the amount of SVF increases which may assist in the fixation of the formulation on the vaginal mucosa. The formulations were able to control about 75% of the released HYP demonstrating a sustained release profile. Finally, all formulations acted as safe vaginal drug delivery systems.

Intravaginal Delivery of Syngonanthus nitens (Bong.) Ruhland Fraction Based on a Nanoemulsion System Applied to Vulvovaginal Candidiasis Treatment.

In this study, was evaluated the chemical composition of a fraction from Syngonanthus nitens extract and its antimicrobial potential unloaded (Fr3) and loaded (F9Fr3) into a nanoemulsion (F9) composed of cholesterol as the oil phase (10%), polyoxyethylene 20-cetyl ether and soy phosphatidylcholine (2:1) as surfactant (20%), and a solution of phosphate buffer (pH 7.4) plus chitosan polymer dispersion (0.25%) as the aqueous phase (70%) to use for VVC treatment. Phytochemical procedures showed that Fr3 is rich in luteolin, which is responsible for the antimicrobial activity. F9 development showed satisfactory parameters for use in the vulvovaginal candidiasis (VVC) treatment, as F9 demonstrated pseudoplastic, elastic behavior, and adhesive properties on vaginal mucosa. In addition, we observed improvement in antimicrobial potential of Fr3 on planktonic and biofilms after incorporation in F9. Fr3 and F9Fr3 showed satisfactory parameters related to toxic profiles in cell lines and in a model of acute toxicity by Artemia salina. The in vivo VVC assay showed that F9Fr3 was more active than unloaded Fr3 in VVC treatment. In conclusion, this work showed that use of a fraction rich in luteolin can be a used as an antimicrobial for treatment of vaginal infections and that use of nanostructured lipid systems was an important factor in the biological efficacy of Fr3, especially in treatment of acute VVC.

New antimycobacterial agents in the pre-clinical phase or beyond: recent advances in patent literature (2001-2016).

INTRODUCTION: Tuberculosis, an infectious disease, has caused more deaths worldwide than any other single infectious disease, killing more than 1.5 million people each year; equating to 4,100 deaths a day. In the past 60 years, no new drugs have been added to the first line regimen, in spite of the fact that thousands of papers have been published on drugs against tuberculosis and hundreds of drugs have received patents as new potential products. Thus, there is undoubtedly an urgent need for the deployment of new effective drugs against tuberculosis. Areas covered: This review brings to the reader the opportunity to understand the chemical and biological characteristics of all patented anti-tuberculosis drugs in North America, Europe, Japan, and Russia. The 116 patents discussed here concern new molecules in the early or advanced phase of development in the last 16 years. Expert opinion: Of all 116 patents, only one developed drug, bedaquiline, is used, and then, only in specific cases. Another three drugs are in clinical studies. However, many other compounds, for which there are in vitro and in vivo studies, seem to fulfil the requisite criteria to be a new anti-tuberculosis agent. However, why are they not in use? Why were so many studies interrupted? Why is there no more news for many of these drugs?