Deciphering the mechanism of action of VP343, an antileishmanial drug candidate, in Leishmania infantum.

Antileishmanial chemotherapy is currently limited due to severe toxic side effects and drug resistance. Hence, new antileishmanial compounds based on alternative approaches, mainly to avoid the emergence of drug resistance, are needed. The present work aims to decipher the mechanism of action of an antileishmanial drug candidate, named VP343, inhibiting intracellular Leishmania infantum survival via the host cell. Cell imaging showed that VP343 interferes with the fusion of parasitophorous vacuoles and host cell late endosomes and lysosomes, leading to lysosomal cholesterol accumulation and ROS overproduction within host cells. Proteomic analyses showed that VP343 perturbs host cell vesicular trafficking as well as cholesterol synthesis/transport pathways. Furthermore, a knockdown of two selected targets involved in vesicle-mediated transport, Pik3c3 and Sirt2, resulted in similar antileishmanial activity to VP343 treatment. This work revealed potential host cell pathways and targets altered by VP343 that would be of interest for further development of host-directed antileishmanial drugs.

Relationship Between Structure And Antimicrobial Activity Of Zinc Oxide Nanoparticles: An Overview.

The inappropriate use of antimicrobials has resulted in the selection of resistant strains. Thus, a great number of studies have focused on the investigation of new antimicrobial agents. The use of zinc oxide nanoparticles (ZnO NPs) to optimise the fight against microbial resistance has been receiving increased attention due to the non-specific activity of inorganic antimicrobial agents. The small particle size and the high surface area of ZnO NPs can enhance antimicrobial activity, causing an improvement in surface reactivity. In addition, surface modifiers covering ZnO NPs can play a role in mediating antimicrobial activity since the surface properties of nanomaterials alter their interactions with cells; this may interfere with the antimicrobial effect of ZnO NPs. The possibility of using surface modifiers with groups toxic to microorganisms can improve the antimicrobial activity of ZnO NPs. Understanding the exact toxicity mechanisms is crucial to elucidating the antimicrobial activity of ZnO NPs in bacteria and fungi. Therefore, this review aims to describe the mechanisms of ZnO NPs toxicity against fungi and bacteria and how the different structural and physical-chemical characteristics of ZnO NPs can interfere in their antimicrobial activity.

The Critical Role of Thioacetamide Concentration in the Formation of ZnO/ZnS Heterostructures by Sol-Gel Process.

ZnO/ZnS heterostructures have emerged as an attractive approach for tailoring the properties of particles comprising these semiconductors. They can be synthesized using low temperature sol-gel routes. The present work yields insight into the mechanisms involved in the formation of ZnO/ZnS nanostructures. ZnO colloidal suspensions, prepared by hydrolysis and condensation of a Zn acetate precursor solution, were allowed to react with an ethanolic thioacetamide solution (TAA) as sulfur source. The reactions were monitored in situ by Small Angle X-ray Scattering (SAXS) and UV-vis spectroscopy, and the final colloidal suspensions were characterized by High Resolution Transmission Electron Microscopy (HRTEM). The powders extracted at the end of the reactions were analyzed by X-ray Absorption spectroscopy (XAS) and X-ray diffraction (XRD). Depending on TAA concentration, different nanostructures were revealed. ZnO and ZnS phases were mainly obtained at low and high TAA concentrations, respectively. At intermediate TAA concentrations, we evidenced the formation of ZnO/ZnS heterostructures. ZnS formation could take place via direct crystal growth involving Zn ions remaining in solution and S ions provided by TAA and/or chemical conversion of ZnO to ZnS. The combination of all the characterization techniques was crucial to elucidate the reaction steps and the nature of the final products.

Drug Delivery Systems Obtained from Silica Based Organic-Inorganic Hybrids.

This is a review of hybrid materials based on silica as an inorganic phase used as drug delivery systems (DDS). Silica based DDS have shown effectivity when compared with traditional delivery systems. They present advantages such as: (a) ability to maintain the therapeutic range with minor variations; (b) prevention of local and systemic toxic effects; (c) plasma concentrations increase of substances with a short half-life; and (d) reduction of the number of daily doses, which may increase patient adherence to the treatment. These advantages occur due to the physical, chemical and optical properties of these materials. Therefore, we discuss the properties and characteristics of them and we present some applications, using different approaches of DDS to ensure therapeutic effectiveness and side effects reduction such as implantable biomaterial, film-forming materials, stimuli-responsive systems and others.