Tuberculosis (TB) is an infectious, airborne disease caused by the bacterium Mycobacterium tuberculosis that mainly affects the lungs. Fortunately,
tuberculosis is a curable disease, and in recent years, death rates for this disease have decreased. However, the existence of
antibiotic-resistant strains and the occurrence of
co-infections with human immunodeficiency virus (HIV), have led to increased mortality in recent years. Another area of concern is that one-third of the world's population is currently infected with M.
tuberculosis in its latent state, serving as a potential reservoir for active TB. In an effort to address the failure of current TB drugs, greater attention is being given to the importance of bioinorganic chemistry as an ally in new research into the development of anti-TB drugs.
Ruthenium (Ru) is a chemical
element that can mimic
iron (Fe) in the body. In previous studies involving the following heteroleptic Ru complexes, [Ru(pic)(dppb)(bipy)]PF6 (
SCAR1), [Ru(pic)(dppb)(Me-bipy)]PF6 (
SCAR2), [Ru(pic)(dppb)(phen)]PF6 (SCAR4), cis-[Ru(pic)(
dppe)2]PF6 (SCAR5), and [Ru(pic)(
dppe)(phen)]PF6 (SCAR7), we observed excellent anti-TB activity, moderate cell-toxicity, and a lack of oral bioavailability in an in vivo model of these complexes. Therefore, the objective of this study was to evaluate the toxicity and oral bioavailability of these complexes by loading them into a nanostructured
lipid system. The nanostructured
lipid system was generated using different ratios of
surfactant (soybean
phosphatidylcholine, Eumulgin®, and
sodium oleate), aqueous phase (
phosphate buffer with a concentration of 1X and pH 7.4), and oil (
cholesterol) to generate a system for the incorporation of Ru(II) compounds. The anti-TB activity of the compounds was determined using a microdilution assay with
Resazurin (REMA) against strains of M.
tuberculosis H37Rv and clinical isolates resistant. Cytotoxicity assay using J774.A1 cells (ATCC TIB-67) and intra-macrophage activity were performed. The oral bioavailability assay was used to analyze blood collected from female BALB/C mice. Plasma collected from the same mice was analyzed via inductively coupled plasma mass spectrometry (ICP-MS) to quantify the number of Ru
ions. The complexes loaded into the nanostructured
lipid system maintained in vitro activity and toxicity was found to be reduced compared with the compounds that were not loaded. The complexes showed intra-macrophagic activity and were orally bioavailable.