Advances in nanocarriers as drug delivery systems in Chagas disease

Chagas disease is one of the most important public health problems in Latin America due to its high mortality and morbidity levels. There is no effective treatment for this disease since drugs are usually toxic with low bioavailability. Serious efforts to achieve disease control and eventual eradication have been unsuccessful to date, emphasizing the need for rapid diagnosis, drug development, and a reliable vaccine. Novel systems for drug and vaccine administration based on nanocarriers represent a promising avenue for Chagas disease treatment. Nanoparticulate systems can reduce toxicity, and increase the efficacy and bioavailability of active compounds by prolonging release, and therefore improve the therapeutic index. Moreover, nanoparticles are able to interact with the host’s immune system, modulating the immune response to favour the elimination of pathogenic microorganisms. In addition, new advances in diagnostic assays, such as nanobiosensors, are beneficial in that they enable precise identification of the pathogen. In this review, we provide an overview of the strategies and nanocarrier-based delivery systems for antichagasic agents, such as liposomes, micelles, nanoemulsions, polymeric and non-polymeric nanoparticles. We address recent progress, with a particular focus on the advances of nanovaccines and nanodiagnostics, exploring new perspectives on Chagas disease treatment

Bioactive bioflavonoids from Platonia insignis (bacuri) residues as added value compounds

Platonia insignis fruit, popularly known as bacuri, is traditionally used in folk medicine for its anti-inflammatory and antioxidant properties. Therefore, this study determined the chemical composition and biological activities of the bacuri’s shell and seeds extracts, considered residues from its consumption and industrial uses. Four biflavonoids (GB-2a, GB-1a, morelloflavone, and volkensiflavone) were identified in the extracts by high-performance liquid chromatography-diode array detection (HPLC-DAD), liquid chromatography tandem mass spectrometry (LC-MS/MS), and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) techniques. Morelloflavone was identified as the main compound in the shell ethyl acetate extract, being responsible for the high in vitro antioxidant (50% effective concentration (EC50) ranging from 8.0-10.5 µg mL−1 in different protocols), anti-glycant (80%), and moderate inhibition of nitric oxide (1.56 µg mL−1 for > 90% cell viability) activities. This extract showed promising in vivo anti-inflammatory activity evaluated through the paw edema protocol after its incorporation into a liquid-crystalline drug carrier system, reducing the edema by up to 31%. The results demonstrated the potential of the fruit for the development of drugs of natural origin and corroborated to add economic value to these discarded residues

A Nanostructured Lipid System to Improve the Oral Bioavailability of Ruthenium(II) Complexes for the Treatment of Infections Caused by Mycobacterium tuberculosis

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

Design, Synthesis and Characterization of N-oxide-containing Heterocycles with In vivo Sterilizing Antitubercular Activity

Tuberculosis, caused by the Mycobacterium tuberculosis (Mtb), is the infectious disease responsible for the highest number of deaths worldwide. Herein, 22 new N-oxide- containing compounds were synthesized followed by in vitro and in vivo evaluation of their antitubercular potential against Mtb. Compound 8 was found to be the most promising compound, with MIC90 values of 1.10 and 6.62 μM against active and non- replicating Mtb, respectively. Additionally, we carried out in vivo experiments to confirm the safety and efficacy of compound 8; the compound was found to be orally bioavailable and highly effective leading to the reduction of the number of Mtb to undetected levels in a mouse model of infection. Microarray-based initial studies on the mechanism of action suggest that compound 8 blocks the process of translation. Altogether, these results indicated benzofuroxan derivative 8 to be a promising lead compound for the development of a novel chemical class of antitubercular drugs

Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil-O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery

Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil—O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery