scholarly journals Biodistribution of Nanostructured Lipid Carriers in Mice Atherosclerotic Model

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3499 ◽  
Author(s):  
Devel ◽  
Almer ◽  
Cabella ◽  
Beau ◽  
Bernes ◽  
...  
Keyword(s):  
Colloidal Stability ◽  
Ex Vivo ◽  
Particle Diameter ◽  
Nanostructured Lipid Carriers ◽  
Atherosclerotic Plaques ◽  
Particle Uptake ◽  
Atherosclerotic Lesions ◽  
Physico Chemical

Atherosclerosis is a major cardiovascular disease worldwide, that could benefit from innovative nanomedicine imaging tools and treatments. In this perspective, we here studied, by fluorescence imaging in ApoE-/- mice, the biodistribution of non-functionalized and RXP470.1-targeted nanostructured lipid carriers (NLC) loaded with DiD dye. RXP470.1 specifically binds to MMP12, a metalloprotease that is over-expressed by macrophages residing in atherosclerotic plaques. Physico-chemical characterizations showed that RXP-NLC (about 105 RXP470.1 moieties/particle) displayed similar features as non-functionalized NLC in terms of particle diameter (about 60-65 nm), surface charge (about −5 — −10 mV), and colloidal stability. In vitro inhibition assays demonstrated that RXP-NLC conserved a selectivity and affinity profile, which favored MMP-12. In vivo data indicated that NLC and RXP-NLC presented prolonged blood circulation and accumulation in atherosclerotic lesions in a few hours. Twenty-four hours after injection, particle uptake in atherosclerotic plaques of the brachiocephalic artery was similar for both nanoparticles, as assessed by ex vivo imaging. This suggests that the RXP470.1 coating did not significantly induce an active targeting of the nanoparticles within the plaques. Overall, NLCs appeared to be very promising nanovectors to efficiently and specifically deliver imaging agents or drugs in atherosclerotic lesions, opening avenues for new nanomedicine strategies for cardiovascular diseases.

scholarly journals Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1838 ◽  
Author(s):  
Jessica Bridoux ◽  
Sara Neyt ◽  
Pieterjan Debie ◽  
Benedicte Descamps ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
High Sensitivity ◽  
Radiochemical Yield ◽  
Control Group ◽  
Complexing Agent ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Pet Ct

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [18F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [18F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE−/− mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [18F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

scholarly journals Amyloid-Targeting PET Tracer [18F]Flutemetamol Accumulates in Atherosclerotic Plaques

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1072 ◽  
Author(s):  
Sanna Hellberg ◽  
Johanna Silvola ◽  
Heidi Liljenbäck ◽  
Max Kiugel ◽  
Olli Eskola ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Mouse Strains ◽  
Aortic Tissue ◽  
Atherosclerotic Plaques ◽  
Carotid Artery Plaque ◽  
Pet Tracer ◽  
Pet Ct ◽  
Human Carotid

Atherosclerosis is characterized by the accumulation of oxidized lipids in the artery wall, which triggers an inflammatory response. Oxidized low-density lipoprotein (ox-LDL) presents amyloid-like structural properties, and different amyloid species have recently been recognized in atherosclerotic plaques. Therefore, we studied the uptake of the amyloid imaging agent [18F]Flutemetamol in atherosclerotic plaques. The binding of [18F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II/LDLR−/−ApoB100/100 mice and C57BL/6N controls. Tracer biodistribution was studied in vivo with PET/CT, and ex vivo by gamma counter and digital ex vivo autoradiography. The presence of amyloid, ox-LDL, and macrophages in the plaques was examined by immunohistochemistry. [18F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II/LDLR−/−ApoB100/100 mice showed large thioflavin-S-positive atherosclerotic plaques containing ox-LDL and macrophages. Autoradiography revealed 1.7-fold higher uptake in the plaques than in a lesion-free vessel wall, but no difference in aortic tissue uptake between mouse strains were observed in the in vivo PET/CT. In conclusion, [18F]Flutemetamol binds to amyloid-positive areas in human atherosclerotic plaques. Further studies are warranted to clarify the uptake mechanisms, and the potential of the tracer for in vivo imaging of atherosclerosis in patients.

scholarly journals Asenapine maleate-loaded nanostructured lipid carriers: optimization and in vitro, ex vivo and in vivo evaluations

Nanomedicine ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. 889-910 ◽  
Author(s):  
Renuka S Managuli ◽  
Julie T Wang ◽  
Farid N Faruqu ◽  
Varun Kushwah ◽  
Sushil Y Raut ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Nanostructured Lipid Carriers

scholarly journals Chemically Modified Biomimetic Carbon-Coated Iron Nanoparticles for Stent Coatings: In Vitro Cytocompatibility and In Vivo Structural Changes in Human Atherosclerotic Plaques

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 802
Author(s):  
Shamil Akhmedov ◽  
Sergey Afanasyev ◽  
Marina Trusova ◽  
Pavel Postnikov ◽  
Yulia Rogovskaya ◽  
...  
Keyword(s):  
Iron Nanoparticles ◽  
Structural Changes ◽  
Cardiovascular Health ◽  
Ex Vivo ◽  
Atherosclerotic Plaques ◽  
Endothelial Cell Culture ◽  
Chemically Modified ◽  
Carbon Coated

Atherosclerosis, a systematic degenerative disease related to the buildup of plaques in human vessels, remains the major cause of morbidity in the field of cardiovascular health problems, which are the number one cause of death globally. Novel atheroprotective HDL-mimicking chemically modified carbon-coated iron nanoparticles (Fe@C NPs) were produced by gas-phase synthesis and modified with organic functional groups of a lipophilic nature. Modified and non-modified Fe@C NPs, immobilized with polycaprolactone on stainless steel, showed high cytocompatibility in human endothelial cell culture. Furthermore, after ex vivo treatment of native atherosclerotic plaques obtained during open carotid endarterectomy surgery, Fe@C NPs penetrated the inner structures and caused structural changes of atherosclerotic plaques, depending on the period of implantation in Wistar rats, serving as a natural bioreactor. The high biocompatibility of the Fe@C NPs shows great potential in the treatment of atherosclerosis disease as an active substance of stent coatings to prevent restenosis and the formation of atherosclerotic plaques.

scholarly journals Bupivacaine-loaded nanostructured lipid carriers prepared with beeswax, lavender or melaleuca oil: characterization and physico-chemical stability

2019 ◽  
Author(s):  
Gabriela Geronimo ◽  
Eneida de Paula ◽  
Gustavo Henrique Rodrigues da Silva ◽  
Lígia Nunes de Morais Ribeiro
Keyword(s):  
Therapeutic Efficacy ◽  
Nanostructured Lipid Carriers ◽  
Physico Chemical ◽  
In Vivo Tests ◽  
Oil Characterization ◽  
New Applications

Although bupivacaine (BVC) is one of the most widely used anesthetics worldwide, improving its therapeutic efficacy without increasing the clinical doses may open possibilities for new applications for this drug. In this study, we prepared innovative formulations: nanostructured lipid carriers (NLC) functionalized with beeswax, lavender or melaleuca oil in order to increase the anesthetic efficiency of BVC. For this, after preparation and characterization of the NLC by dynamic light scattering and determination of the encapsulation efficiency (% EE), stability was monitored during 12 months. The NLC showed appropriate physical-chemical features, with high %EE and stability. The developed formulations proved to be good candidates to increase the therapeutic efficacy of BVC so that further in vitro and in vivo tests are under course to evaluate their advantages, in comparison to the commercial BVC formulation.

scholarly journals Cell-Based Models for Development of Antiatherosclerotic Therapies

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Emile R. Zakiev ◽  
Nikita G. Nikiforov ◽  
Alexander N. Orekhov
Keyword(s):  
Ex Vivo ◽  
Cardiovascular Disorder ◽  
Atherosclerotic Plaques ◽  
Cell Models ◽  
Atherosclerosis Progression ◽  
Synthetic Drugs ◽  
Atherosclerotic Lesions ◽  
Plaque Development ◽  
Atherosclerosis Development

The leading cause of death worldwide is cardiovascular disease. Among the conditions related to the term, the most prominent one is the development of atherosclerotic plaques in the walls of arteries. The situation gets even worse with the fact that the plaque development may stay asymptomatic for a prolonged period of time. When it manifests as a cardiovascular disorder, it is already too late: the unfortunate individual is prescribed with a plethora of synthetic drugs, which are of debatable efficacy in the prevention of atherosclerotic lesions and safety. Cell models could be useful for the purpose of screening substances potentially effective against atherosclerosis progression and effective in reduction of already present plaques. In this overview, we present studies making use of in vitro and ex vivo models of atherosclerosis development that can prove valuable for clinical applications.

scholarly journals Preclinical Assessment of Ursolic Acid Loaded into Nanostructured Lipid Carriers in Experimental Visceral Leishmaniasis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 908
Author(s):  
Jéssica Adriana Jesus ◽  
Ilza Maria Oliveira Sousa ◽  
Thays Nicolli Fragoso da Silva ◽  
Aurea Favero Ferreira ◽  
Márcia Dalastra Laurenti ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Colloidal Stability ◽  
Morphological Changes ◽  
Spherical Shape ◽  
Nanostructured Lipid Carriers ◽  
Liver Preservation ◽  
High Degree ◽  
Low Solubility

Ursolic acid, a triterpene produced by plants, displayed leishmanicidal activity in vitro and in vivo; however, the low solubility of this triterpene limits its efficacy. To increase the activity of ursolic acid (UA), this triterpene was entrapped in nanostructured lipid carriers (UA-NLC), physical-chemical parameters were estimated, the toxicity was assayed in healthy golden hamsters, and the efficacy of UA-NLC was studied in experimental visceral leishmanisis. UA-NLC exhibited a spherical shape with a smooth surface with a size of 266 nm. UA-NLC displayed low polydispersity (PDI = 0.18) and good colloidal stability (−29.26 mV). Hamsters treated with UA-NLC did not present morphological changes in visceral organs, and the levels of AST, ALT, urea and creatinine were normal. Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, animals treated with UA or Amphotericin B (AmB). The therapeutic activity of UA-NLC was associated with the increase in a protective immune response, and it was associated with a high degree of spleen and liver preservation, and the normalization of hepatic and renal functions. These data indicate that the use of lipid nanoparticles as UA carriers can be an interesting strategy for the treatment of leishmaniasis.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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