Nanomechanical testing of drug activities at the cellular level: Case study for endothelium-targeted drugs

Kołodziejczyk, Agnieszka; Targosz‐Korecka, Marta; Szymoński, Marek

doi:10.1016/j.pharep.2017.06.007

Cited by 10 publications

(3 citation statements)

References 24 publications

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“…It was observed that the SMV and CnO amounts had a significantly negative effect on IL-6 levels, whereas the Smix ratio had a significantly positive effect on the same parameter (p < 0.0001). The decrease in IL-6 levels observed with an increase in the SMV amount could be referred to as an SMV antiinflammatory characteristic [38]. It is well established that statins can lower the production of proinflammatory cytokines [39] by inhibiting HMG-CoA reductase, which would activate the mevalonate pathway.…”

Section: Interleukin-6 Measurementsmentioning

confidence: 99%

Coconut Oil Nanoemulsion Loaded with a Statin Hypolipidemic Drug for Management of Burns: Formulation and In Vivo Evaluation

et al. 2020

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Burn wound healing is a complex process that involves the repair of injured tissues and the control of infection to diminish the scar formation, pain, and discomfort associated with such injuries. The aim of this research was to formulate and optimize a self-nanoemulsion drug delivery system based on the use of coconut oil and loaded with simvastatin. Coconut oil possesses antiinflammatory and antibacterial activity, and simvastatin has interesting properties for promoting the wound-healing process because it increases the production of the vascular endothelial growth factor at the site of injury. The Box–Behnken design was employed for the optimization of the coconut oil–simvastatin self-nanoemulsion drug delivery system. The prepared formulations were characterized according to globular size and their activity in the healing of burn wounds by assessing the mean wound diameter and level of interlukin-6 in experimental animals. Additionally, the antimicrobial activity of the prepared formulations was assessed. The nanoemulsion was considered adequately formed when it had droplets of between 65 and 195 nm. The statistical design proved the important synergistic effect of coconut oil and simvastatin for burn wound management in their synergistic potentiation of wound closure and their anti-inflammatory and antimicrobial effects. The optimum formulation achieved up to a 5.3-fold decrease in the mean burn wound diameter, a 4.25-fold decrease in interleukin-6 levels, and a 6-fold increase in the inhibition zone against Staphylococcus aureus when compared with different control formulations. Therefore, the designed nanoemulsions containing a combination of coconut oil and simvastatin could be considered promising platforms for the treatment of chronic and burn wounds.

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Section: Interleukin-6 Measurementsmentioning

confidence: 99%

Coconut Oil Nanoemulsion Loaded with a Statin Hypolipidemic Drug for Management of Burns: Formulation and In Vivo Evaluation

et al. 2020

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“…AFS was used in the broadly understood nano‐diagnosis in cancer cell, which shows higher elasticity of tumor cells compared with normal cells. Additionally, force spectroscopy can be useful to detect changes in the mechanical phenotype of various cell lines affected by hormones, high glucose level, cytokines, or drugs . Using force spectroscopy, one can obtain maps of the elasticity modulus within a single cell or tissue .…”

Section: Introductionmentioning

confidence: 99%

Sensing of silver nanoparticles on/in endothelial cells using atomic force spectroscopy

Kołodziejczyk¹,

Jakubowska²,

Kucińska³

et al. 2018

J of Molecular Recognition

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Endothelial cells, due to their location, are interesting objects for atomic force spectroscopy study. They constitute a barrier between blood and vessel tissues located deeper, and therefore they are the first line of contact with various substances present in blood, eg, drugs or nanoparticles. This work intends to verify whether the mechanical response of immortalized human umbilical vein endothelial cells (EA.hy926), when exposed to silver nanoparticles, as measured using force spectroscopy, could be effectively used as a bio-indicator of the physiological state of the cells. Silver nanoparticles were characterized with transmission electron microscopy and dynamic light scattering techniques. Tetrazolium salt reduction test was used to determine cell viability after treatment with silver nanoparticles. An elasticity of native cells was examined in the Hanks' buffer whereas fixed cells were softly fixed with formaldehyde. Additional aspect of the work is the comparative force spectroscopy utilizing AFM probes of ball-shape and conical geometries, in order to understand what changes in cell elasticity, caused by SNPs, were detectable with each probe. As a supplement to elasticity studies, cell morphology observation by atomic force microscopy and detection of silver nanoparticles inside cells using transmission electron microscopy were also performed. Cells exposed to silver nanoparticles at the highest selected concentrations (3.6 μg/mL, 16 μg/mL) are less elastic. It may be associated with the reorganization of the cellular cytoskeleton and the "strengthening" of the cell cortex caused by presence of silver nanoparticles. This observation does not depend on cell fixation. Agglomerates of silver nanoparticles were observed on the cell membrane as well as inside the cells.

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“…In particular, statins exert anti-inflammatory properties [ 7 ] and inhibit that of the proinflammatory cytokines [ 8 ]. The anti-inflammatory effect of statins has been attributed to their ability to reduce, by inhibiting HMG-CoA reductase, not only cholesterol synthesis but also the activation of the mevalonate pathway, with the consequent reduction of isoprenylated and geranylgeranylated proteins, and in particular of Ras prenylation.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia

Barale

Frascaroli

Senkeev

et al. 2018

BioMed Research International

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Background Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation. MethodsIn hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1β, -5, -6, -7, -8, -9, -10, -12, and -13, IFN-γ, IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2'-deoxyguanosine). Results After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p<0.0001), IFN-γ (p<0.0001), VEGF (p<0.0001), sE-selectin (p<0.0001), sCD-40L (p<0.0001), sP-selectin (p=0.003), and 8-OH-2'-deoxyguanosine (p<0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN-γ, E-selectin, sCD-40L, 8-OH-2'-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity. Conclusion In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis.

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Nanomechanical testing of drug activities at the cellular level: Case study for endothelium-targeted drugs

Cited by 10 publications

References 24 publications

Coconut Oil Nanoemulsion Loaded with a Statin Hypolipidemic Drug for Management of Burns: Formulation and In Vivo Evaluation

Coconut Oil Nanoemulsion Loaded with a Statin Hypolipidemic Drug for Management of Burns: Formulation and In Vivo Evaluation

Sensing of silver nanoparticles on/in endothelial cells using atomic force spectroscopy

Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia

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