A Nanostructured Lipid System to Improve the Oral Bioavailability of Ruthenium(II) Complexes for the Treatment of Infections Caused by Mycobacterium tuberculosis
Abstract: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 infe… Show more
“…This formulation demonstrated enhanced antimicrobial activity against M. tuberculosis [156]. For ruthenium complexes, incorporation into the NLC struc-ture resulted in increased bioavailability of ruthenium along with reduced toxicity [157].…”
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Cell Signaling pathways form an integral part of our existence, that allows the cells to comprehend a stimulus and respond back. Such reactions, to external cues from the environment, are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people who are asthmatic, 65 million who are suffering from COPD, 2.3 million who are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and nation annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.
“…This formulation demonstrated enhanced antimicrobial activity against M. tuberculosis [156]. For ruthenium complexes, incorporation into the NLC struc-ture resulted in increased bioavailability of ruthenium along with reduced toxicity [157].…”
:
Cell Signaling pathways form an integral part of our existence, that allows the cells to comprehend a stimulus and respond back. Such reactions, to external cues from the environment, are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people who are asthmatic, 65 million who are suffering from COPD, 2.3 million who are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and nation annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.
“…Likewise, Da Silva et al [ 303 ] investigated the antimycobacterial efficacy of Ru(II) heteroleptic compounds, known as SCARs. They found that these compounds maintain their efficacy when encapsulated in SLNs (labeled SCAR-SLN, composed of 10 % cholesterol, 10 % phosphatidylcholine, sodium oleate, and Eumulgin HRE 40, with 80 % of the formulation being phosphate buffer).…”
Section: Nanoscale Drug Delivery Systemsmentioning
confidence: 99%
“… Fig. 10 A) Temporal plasma concentration profile of Scar2-loaded NLS following a single oral administration via gavage at a dose of 300 mg/kg body weight, B) Intramacrophage activity of Scar-loaded nanosystems [ 303 ]. Reprint published from open access article by Frontiers Media S.A.…”
Section: Nanoscale Drug Delivery Systemsmentioning
“…Colorimetric readings were performed on the spectrophotometer at 570 and 600 nm. Gentian violet (Synth, São Paulo, SP, Brazil) was used as the reference cytotoxic drug (Meira et al, 2017;Da Silva et al, 2018). EC 50 values were determined from data-points gathered from three independent experiments by using Graph Pad Prism version 5.01 (Graph Pad Software, San Diego, CA, United States).…”
Leishmaniasis are group of neglected diseases with worldwide distribution that affect about 12 million people. The current treatment is limited and may cause severe adverse effects, and thus, the search for new drugs more effective and less toxic is relevant. We have previously investigated the immunomodulatory effects of LASSBio-1386, an N-acylhydrazone derivative. Here we investigated the in vitro and in vivo activity of LASSBio-1386 against L. amazonensis. LASSBio-1386 inhibited the proliferation of promastigotes of L. amazonensis (EC50 = 2.4 ± 0.48 µM), while presenting low cytotoxicity to macrophages (CC50 = 74.1 ± 2.9 µM). In vitro incubation with LASSBio-1386 reduced the percentage of Leishmania-infected macrophages and the number of intracellular parasites (EC50 = 9.42 ± 0.64 µM). Also, in vivo treatment of BALB/c mice infected with L. amazonensis resulted in a decrease of lesion size, parasitic load and caused histopathological alterations, when compared to vehicle-treated control. Moreover, LASSBio-1386 caused ultrastructural changes, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of L. amazonensis. Aiming to its possible molecular interactions, we performed docking and molecular dynamics studies on Leishmania phosphodiesterase B1 (PDB code: 2R8Q) and LASSBio-1386. The computational analyses suggest that LASSBio-1386 acts against Leishmania through the modulation of leishmanial PDE activity. In conclusion, our results indicate that LASSBio-1386 is a promising candidate for the development of new leishmaniasis treatment.
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