Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart

Barbieri, Lucas Regatieri; Lourenço-Filho, Domingos D.; Tavares, Elaine Rufo; Carvalho, Priscila O.; Gutierrez, Paulo Sampaio; Maranhão, Raul C.; Stolf, Noedir Antônio Groppo

doi:10.1016/j.athoracsur.2016.12.044

Cited by 14 publications

(18 citation statements)

References 23 publications

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“…Four hours after ischemic induction, animals were intravenously treated LDE-MTX or unconjugated LDE in the concentration of 1 mg/kg. This LDE-MTX dose afforded considerable anti-inflammatory and tissue protective effects in experimental models of arthritis (Mello et al, 2013) and myocardial infarction (Maranhao et al, 2017) in our previous studies.…”

Section: Lde-mtxc Treatmentmentioning

confidence: 50%

“…We have investigated the anti-inflammatory and neuroprotective effects of LDE-MTX in an experimental model of cortical ischemia, as previous studies reported promising anti-inflammatory and tissue protective actions of LDE-MTX following experimental arthritis (Mello et al, 2013), myocardial infarction (Maranhao et al, 2017) and other diseases Barbieri et al, 2017;Fiorelli et al, 2017;Gomes et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…We have developed an emulsion lipid system composed of nanoparticles of medium size 30 nm (LDE) functionally similar to low density lipoprotein (LDL), but with different protein composition, which allows more efficient internalization into the cells (Maranhao et al, 1993). LDE has been used as an efficient carrier for the transport of anti-inflammatory and chemotherapeutic substances, including docetaxel (Meneghini et al, 2019), carmustine (Daminelli et al, 2016), paclitaxel (Maranhão et al, 2008 and methotrexate (MTX) Mello et al, 2013;Maranhao et al, 2017) in different experimental models of non-neural diseases and even in a clinical trial for epithelial ovarian carcinoma in humans (Graziani et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Methotrexate carried in lipid core nanoparticles reduces microglial activation and is neuroprotective after ischemic cortical stroke

Pereira¹,

Dias

Santos

et al. 2020

Preprint

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Methotrexate carried in lipid core nanoparticles (LDE-MTX) is a low toxicity compound effective in reducing inflammation and secondary damage in experimental models of arthritis, atherosclerosis, myocardial infarction, cardiac allograft vasculopathy and other pathological conditions. Nevertheless, whether it is neuroprotective after stroke is unknown. Here, we explored whether LDE-MTX could cross blood brain barrier (BBB) to exert anti-inflammatory and neuroprotecive effects after experimental cortical stroke in rats. Tissue uptake was assessed by injecting radioactively labeled-LDE through the caudal vein into both sham (n=18) and adult Wistar rats submitted to endothelin-1 (ET-1)-induced cortical stroke (n=11). To address possible neuroprotective effects of LDE-MTX after stroke, 10 adult male Wistar rats were randomly allocated in two groups: animals treated with LDE-MTX (1 mg/kg, i.v., n=5) or LDE-alone (i.v., n=5) at 4 hours after stroke induction. Animals were perfused with 0.9% saline and 4% paraformaldehyde at 7 days post-injury. Histopathology was assessed by cresyl violet staining. Mature neuronal bodies (anti-NeuN), astrocytes (anti-GFAP) and microglia (anti-Iba1) were immunolabeled by immunohistochemistry.Scintigraphy technique revealed accumulation of tritiated LDE in different brain regions and in non-neural organs without overt toxicity in both sham and ischemic rats. LDE-MTX treatment induced a 10-fold (1000%) reduction in microglial activation in the ischemic cortex and afforded a 319% increase in neuronal preservation in the ischemic periinfarct region compared to LDE-alone group. There was no effect of LDE-MTX treatment on primary infarct area and astrocytosis. The results suggest that LDE-MTX formulation must be considered a very promising neuroprotective agent for ischemic stroke. Future studies using different concentrations and longer survival times are needed before assessing the suitability of LDE-MTX as a neuroprotective agent for human stroke.

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Section: Lde-mtxc Treatmentmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Methotrexate carried in lipid core nanoparticles reduces microglial activation and is neuroprotective after ischemic cortical stroke

Pereira¹,

Dias

Santos

et al. 2020

Preprint

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“…Various studies suggest that systemic delivery of nanoparticles and emulsions containing chemotherapeutics concentrated in a transplanted heart can prevent vasculopathy 25,26. Yet others advocate for the use of nanoparticles decorated with immunotherapeutics as a delivery device for tissues such as allo-islets to allow for implantation under the shield of immunomodulating therapeutics 27.…”

Section: Discussionmentioning

confidence: 99%

“…Along with pre-treatment strategies, delivery mechanisms intended to allow for organ level immunosuppression while leaving the patient's global immune system intact may represent the future of organ specific immunosuppression. These disruptive technologies include micro and nanoparticles carrying immunosuppressants and chemotherapeutics, for example, delivered both systemically and directly to an organ allograft 25,26,28…”

Section: Discussionmentioning

confidence: 99%

Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

et al. 2018

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Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives

Pan,

Chen,

Yang

2023

CURR MED SCI

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Atherosclerosis (AS) is characterized by impairment and apoptosis of endothelial cells, continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells, which is documented as the traditional cellular paradigm. However, the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis, transdifferentiation and novel cell death forms such as ferroptosis, pyroptosis, and extracellular trap were reported. Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets. On the other side, the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden. Stem cell- or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects. Given the complexity of pathological changes of AS, attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging. In this review, the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation. The future challenges and improvements were also discussed.

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Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart

Cited by 14 publications

References 23 publications

Methotrexate carried in lipid core nanoparticles reduces microglial activation and is neuroprotective after ischemic cortical stroke

Methotrexate carried in lipid core nanoparticles reduces microglial activation and is neuroprotective after ischemic cortical stroke

Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives

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