Novel dual ROS-sensitive and CD44 receptor targeting nanomicelles based on oligomeric hyaluronic acid for the efficient therapy of atherosclerosis

Hou, Xiaoya; Lin, Hua; Zhou, Xiudi; Cheng, Ziting; Li, Yi; Lü, Xue; Zhao, Feng; Zhu, Yan‐Ping; Zhang, Peng; Chen, Daquan

doi:10.1016/j.carbpol.2019.115787

Cited by 54 publications

(43 citation statements)

References 28 publications

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“… 22 , 23 , 54 Furthermore, Hou et al demonstrated that the treatment of high fat diet-fed rats with curcumin enclosed in CD44-specific HA-based micelles for 2 weeks reduced the area of atherosclerotic lesions in rats’ aortas supporting a possibility of the vascular delivery of HA-based nanocarriers. 55 Accordingly, hypotensive effects of HyC12-Cur observed in this study, as well as the detection of HyFC10-PFOB components in rat aortas, might indeed be due to the HA–based uptake of HyC12-based nanocapsules to the vascular wall.…”

Section: Discussionmentioning

confidence: 52%

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

Czyżyńska-Cichoń¹,

Janik-Hazuka²,

Szafraniec-Szczęsny³

et al. 2021

IJN

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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.

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Section: Discussionmentioning

confidence: 52%

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

Czyżyńska-Cichoń¹,

Janik-Hazuka²,

Szafraniec-Szczęsny³

et al. 2021

IJN

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“…Andrographolide exhibits great anti-inflammatory activity and the antioxidant activity of PEG-PPS was endowed by the thioether in the hydrophobic block PPS. Another research has reported a novel dual ROS-sensitive and CD44 receptors targeting nanocarriers composed of oligomeric hyaluronic acid-2′-[propane-2, 2-diyllbls (thio)] diacetic acl-hydroxymethylferrocene (HASF) [ 20 ]. Curcumin was encapsulated into HASF and provided potent anti-inflammatory and antioxidant effects.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis

et al. 2020

J Nanobiotechnol

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Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis.

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“…After up-regulating ABCA1 expression and inhibiting SR-A and CD36 in macrophages, curcumin reduced ROS production and foam cell formation to stabilize vulnerable plaques ( Soltani et al, 2017 ). Curcumin analogs, such as L3, tetrahydrocurcumin (THC), Cur-NPs( Meng et al, 2019 ), HASF (a dual ROS-sensitive and CD44 receptor targeting amphiphilic carrier) ( Hou et al, 2020 ), and curcumin compounds, are synthetic compounds that have similar effects; for example, they elevate glutathione peroxidase (GPx) catalyze GSH, and have higher bioavailability than common curcumin, showing anti-oxidative stress in atherosclerosis through multiple gene targets ( Naito et al, 2002 ; Huang et al, 2015 ; Zheng et al, 2016 ). In summary, the antioxidant effects of curcumin combat atherosclerosis by the following mechanisms: 1) Blocking enzymes that promote ROS generation; 2) increasing antioxidant enzyme activity; 3) reducing damage to endothelial cells by anti-inflammatory actions, enhancing eNOS, and reducing adhesion factors; and 4) reducing foam cell formation (more details in Table 2 ).…”

Section: Tcm For Treatment Of Atherosclerosis Targeting Oxidative Stressmentioning

confidence: 99%

Chinese Herbal Medicines and Active Metabolites: Potential Antioxidant Treatments for Atherosclerosis

et al. 2021

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Atherosclerosis is a complex chronic disease that occurs in the arterial wall. Oxidative stress plays a crucial role in the occurrence and progression of atherosclerotic plaques. The dominance of oxidative stress over antioxidative capacity generates excess reactive oxygen species, leading to dysfunctions of the endothelium and accelerating atherosclerotic plaque progression. Studies showed that Chinese herbal medicines and traditional Chinese medicine (TCM) might regulate oxidative stress; they have already been used to treat diseases related to atherosclerosis, including stroke and myocardial infarction. This review will summarize the mechanisms of oxidative stress in atherosclerosis and discuss studies of Chinese herbal medicines and TCM preparations treating atherosclerosis, aiming to increase understanding of TCM and stimulate research for new drugs to treat diseases associated with oxidative stress.

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Novel dual ROS-sensitive and CD44 receptor targeting nanomicelles based on oligomeric hyaluronic acid for the efficient therapy of atherosclerosis

Cited by 54 publications

References 28 publications

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

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

Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis

Chinese Herbal Medicines and Active Metabolites: Potential Antioxidant Treatments for Atherosclerosis

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