Nanostructured Lipid Systems as a Strategy to Improve the in Vitro Cytotoxicity of Ruthenium(II) Compounds

Abstract

Abstract:Tuberculosis is an ancient disease that is still present as a global public health problem. Our group has been investigating new molecules with anti-TB activity. In this context, inorganic chemistry has been a quite promising source of such molecules, with excellent results seen with ruthenium compounds. Nanostructured lipid systems may potentiate the action of drugs by reducing the required dosage and side effects and improving the antimicrobial effects. The aim of this study was to develop a nanostructured lipid system and then characterize and apply these encapsulated compounds (SCARs 1, 2 and 4) with the goal of improving their activity by decreasing the Minimum Inhibitory Concentration (MIC 90 ) and reducing the cytotoxicity (IC 50 ). The nanostructured system was composed of 10% phase oil (cholesterol), 10% surfactant (soy oleate, soy phosphatidylcholine and Eumulgin ® ) and 80% aqueous phase (phosphate buffer pH = 7.4). Good activity against Mycobacterium tuberculosis was maintained after the incorporation of the compounds into the nanostructured lipid system, while the cytotoxicity decreased dramatically, in some cases up to 20 times less toxic than the unencapsulated drug.

Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity

“…To ensure greater stability and improved solubility, compound 8 was evaluated in an in vivo assay using a pharmaceutical formulation. The nanostructured lipid system (ME) was synthesized as described by our group previously, 64 with the following composition: 10% oil phase (cholesterol), 10% surfactant (a mixture of soy phosphatidylcholine, sodium oleate, and Eumulgin HRE 40 [polyoxyl 40 castor oil-hydrogenated]; 3:6:8), and 80% aqueous phase (phosphate buffer, pH 7.4). The compounds studied were incorporated at the desired concentration for the in vivo experiments by mass solubilization at the respective volume and sonicated for 3 min in batch mode at 15% amplitude.…”

In Vitro Activity of Copper(II) Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis

“…The increase in the antimycobacterial activity of the NLS seems to occur at the level of the mycobacterial plasma membrane. The interaction between the NLS and the membrane results in the de-structuration of a phospholipid bilayer, thereby affecting its fluidity, in turn leading to cell death [ 14 , 33 ].…”

“…The NLS’s were prepared as described by Formariz et al and Freitas et al [ 14 , 36 , 37 ] with the following composition: 10% oil phase ( i.e. , cholesterol), 10% surfactant ( i.e.…”

“…Many studies have shown the potential of pharmaceutical nanotechnology in the treatment, prevention, and diagnosis of several pathologies, including TB [ 13 ]. The use of nanotechnology for the development of new drugs against tuberculosis aims for (a) protection of the compound in the therapeutic system against possible instability in the organism, promoting the maintenance of plasma levels at constant concentration; (b) increased therapeutic efficacy; (c) the progressive and controlled release of the drug by conditioning the environmental stimuli (sensitive to the pH variation or temperature); (d) the expressive reduction of toxicity by the reduction of peak plasma levels of maximum concentration; (e) reducing the instability and decomposition of sensitive compounds; (f) the possibility of the orientation to specific targets (site specificity); (g) the incorporation of hydrophilic or lipophilic substances in the devices; and (h) the reduction of therapeutic dose and the number of administrations and an increase in patient acceptance of therapy [ 14 ].…”

Special Issue on Ruthenium Complexes

“…In particular, the crucial importance of the chemical structure of these ruthenium complexes for their vascular effects has been emphasized. Fernando Rogério Pavan et al [ 12 ] reported on the in vitro anti-tuberculosis activity and cytotoxicity of ruthenium compounds encapsulated in nanostructured lipid systems composed of cholesterol, surfactant, and aqueous phase. Finally, Claudio L. Donnici [ 13 ] investigated the in vitro antifungal activity of a series of ruthenium dithiocarbamate complexes against different fungal species of clinical interest and related to invasive fungal infections.…”