2017

DOI: 10.2147/ijn.s124252

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Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy

Mengyuan Zhang¹,

Cuiping Jiang³

et al.

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Introduction2

Rhdl Nanoparticles As a Drug Delivery Vehicle1

Cddo-me-nps1

Clinically Available Pharmaceutical Treatments1

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Cited by 73 publications

(44 citation statements)

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“… 19–21 Moreover, there is a growing interest in targeting hyaluronan-based delivery systems against eg atherosclerosis taking advantage of receptors for hyaluronic acid. 22 , 23 However, despite many different approaches, the smart delivery of lipophilic vasoprotective molecules to the vascular wall remains a challenge including the difficulties to track their vascular delivery. 5 …”

Section: Introductionmentioning

confidence: 99%

Low Dose Curcumin Administered in Hyaluronic Acid-Based Nanocapsules Induces Hypotensive Effect in Hypertensive Rats

Czyżyńska-Cichoń¹,

Janik-Hazuka²,

Szafraniec-Szczęsny³

et al. 2021

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Background Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. Methods The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic – DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. Results In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur – based treatment changes in SBP, DBP and MAP amounted to −2.0±0.8 mmHg, −3.9±0.7 mmHg and −3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19 F NMR technique after a single intragastric administration. Conclusion These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.

“… 19–21 Moreover, there is a growing interest in targeting hyaluronan-based delivery systems against eg atherosclerosis taking advantage of receptors for hyaluronic acid. 22 , 23 However, despite many different approaches, the smart delivery of lipophilic vasoprotective molecules to the vascular wall remains a challenge including the difficulties to track their vascular delivery. 5 …”

Section: Introductionmentioning

confidence: 99%

Low Dose Curcumin Administered in Hyaluronic Acid-Based Nanocapsules Induces Hypotensive Effect in Hypertensive Rats

Czyżyńska-Cichoń¹,

Janik-Hazuka²,

Szafraniec-Szczęsny³

et al. 2021

View full text Add to dashboard Cite

Background Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. Methods The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic – DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. Results In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur – based treatment changes in SBP, DBP and MAP amounted to −2.0±0.8 mmHg, −3.9±0.7 mmHg and −3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19 F NMR technique after a single intragastric administration. Conclusion These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.

“…Chronic inflammation is involved in the development of luminal thrombosis [3], due to its role in exacerbating endothelial injury and provoking atherosclerotic plaque rupture [2, 4]. However, current antiatherosclerotic agents and antiplatelet therapy only prevent the physical formation of thrombosis [5, 6], but do not alleviate inflammation or endothelial dysfunction. Thus, developing new strategies aimed at protecting against inflammation and endothelial dysfunction may have important clinical implications in antithrombotic therapies.…”

Section: Introductionmentioning

confidence: 99%

Yiqi-Huoxue Granule (YQHX) Downregulates Prothrombotic Factors by Modulating KLF2 and NF-κB in HUVECs following LPS Stimulation

¹

,

²

,

³

et al. 2019

Oxidative Medicine and Cellular Longevity

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The Yiqi-Huoxue granule (YQHX) is a traditional Chinese medication widely used in the therapy of the traditional Chinese medicine diagnosis “Qi deficiency” or “blood stasis” in China. Both these symptoms are related to inflammation, but the mechanisms of YQHX against inflammation are largely unknown. Thus, our present study investigated the effects of YQHX on regulating inflammatory responses induced by lipopolysaccharides (LPS) in HUVECs. Our data found that YQHX remarkably inhibits the production of prothrombotic factors, plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF), while it upregulates the protein expression of Kruppel-like factor 2 (KLF2). The increase in PAI-1 and TF was significantly attenuated through a transgenic knockdown in KLF2 with a Lenti-shKLF2 vector. YQHX also decreases the phosphorylation of nuclear factor-κB (NF-κB) p65 and IκB following LPS stimulation, and it effectively suppresses PAI-1 and TF via a NF-κB-dependent mechanism. Taken together, our results suggest that YQHX provides a notable antithrombotic activity via regulating the KLF2 expression and NF-κB signaling pathway in HUVECs. The KLF2 and NF-κB may be potential therapeutic targets for interventions of inflammation associated with atherosclerosis.

“…The application of rHDL nanoparticles for delivering therapeutic compounds for the treatment of cancer has been studied extensively [76][77][78]. Recent studies show that rHDL nanoparticle serve as a drug delivery system to deliver compounds efficiently into macrophages and atherosclerotic plaques [79]. To investigate the immunomodulatory drugs for atherosclerosis, several nanoparticles were developed to increase the specificity of the drug delivery.…”

Section: Rhdl Nanoparticles As a Drug Delivery Vehiclementioning

confidence: 99%

Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery

¹

,

²

,

³

et al. 2020

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Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear.

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