Cardiovascular diseases (CVDs) are one of the foremost causes of high morbidity and mortality globally. Preventive, diagnostic, and treatment measures available for CVDs are not very useful, which demands promising alternative methods. Nanoscience and nanotechnology open a new window in the area of CVDs with an opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues. The application of nanoparticles and nanocarriers in the area of cardiology has gathered much attention due to the properties such as passive and active targeting to the cardiac tissues, improved target specificity, and sensitivity. It has reported that more than 50% of CVDs can be treated effectively through the use of nanotechnology. The main goal of this review is to explore the recent advancements in nanoparticle-based cardiovascular drug carriers. This review also summarizes the difficulties associated with the conventional treatment modalities in comparison to the nanomedicine for CVDs.

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Nanoparticle-Mediated Drug Delivery for the Treatment of Cardiovascular Diseases.

Hirudin, an acidic polypeptide secreted by the salivary glands of Hirudo medicinalis (also known as “Shuizhi” in traditional Chinese medicine), is the strongest natural specific inhibitor of thrombin found so far. Hirudin have been demonstrated to possess potent anti-thrombotic effect in previous studies. Recently, increasing researches have focused on the anti-thrombotic activity of the derivatives of hirudin, mainly because these derivatives have stronger antithrombotic activity and lower bleeding risk. Additionally, various bioactivities of hirudin have been reported as well, including wound repair effect, anti-fibrosis effect, effect on diabetic complications, anti-tumor effect, anti-hyperuricemia effect, effect on cerebral hemorrhage, and others. Therefore, by collecting and summarizing publications from the recent two decades, the pharmacological activities, pharmacokinetics, novel preparations and derivatives, as well as toxicity of hirudin were systematically reviewed in this paper. In addition, the clinical application, the underlying mechanisms of pharmacological effects, the dose-effect relationship, and the development potential in new drug research of hirudin were discussed on the purpose of providing new ideas for application of hirudin in treating related diseases.

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Pharmacological Activities and Mechanisms of Hirudin and Its Derivatives - A Review.

Thrombosis is a global health issue and one of the leading factors of death. However, its diagnosis has been limited to the late stages, and its therapeutic window is too narrow to provide reasonable and effective treatment. In addition, clinical thrombolytics suffer from a short half-life, allergic reactions, inactivation, and unwanted tissue hemorrhage. Nano-medicines have gained extensive attention in diagnosis, drug delivery, and photo/sound/magnetic-theranostics due to their convertible properties. Furthermore, diagnosis and treatment of thrombosis using nano-medicines have also been widely studied. This review summarizes the recent advances in this area, which revealed six types of nanoparticle approaches: (1) in vitro diagnostic kits using "synthetic biomarkers"; (2) in vivo imaging using nano-contrast agents; (3) targeted drug delivery systems using artificial nanoparticles; (4) microenvironment responsive drug delivery systems; (5) drug delivery systems using biological nanostructures; and (6) treatments with external irradiation. The investigations of nano-medicines are believed to be of great significance, and some of the advanced drug delivery systems show potential applications in clinical theranotics.

/pdf/nano-medicine-for-thrombosis-a-precise-diagnosis-and-4levn4l0xy.pdf

Nano-Medicine for Thrombosis: A Precise Diagnosis and Treatment Strategy

Mechanisms of thrombosis and research progress on targeted antithrombotic drugs.

Recent advances on nanoparticle-based therapies for cardiovascular diseases.

This study proposed a new nonviral gene delivery system for thrombus targeting therapy based on PEGlyation polyamides dendrimer (PAMAM) modified with RGDyC to condense the pDNA with recombinant hirudine (rHV) gene (RGDyC-rHV-EGFP). The RGDyC-mPEG-PAMAM was synthesized and characterized by 1H NMR, PAMAM/pDNA was characterized by particle size, zeta potential, cellular uptake, and gel retraction assay. The transfection was carried out between lipofectamine 2000 and PAMAM/pDNA on HUVEC cells at various N/P ratios. The antithrombotic effect in vivo was evaluated by venous thrombosis model on Wistar rats. It showed that the drug delivery system of RGDyC modified PAMMA, which entrapped pDNA could significantly improve the transfection efficiency. It was about 7.56-times higher than that of lipofectamine 2000. In addition, the expression level of hirudine fusion protein was the highest at N/P ratio of 0.5. The results of antithrombotic effect showed that the weight of thrombus was reduced in RGDyC modified group; compared with heparin group, there was no significant difference ( P > 0.05). Overall, we take the advantage of the unique advantages of hirudine, combining the genetic engineering, nanocarriers, and targeting technology, to achieve the targeted enrichment and activation the hirudine fusion protein in the thrombus site, to improve the concentration of drugs in the thrombus site, finally increasing the curative effect and reduce the risk of bleeding. The strategy of gene delivery system holds unique properties as a gene delivery system and has great promises in thrombus targeting therapy.

Novel Strategy of Gene Delivery System Based on Dendrimer Loaded Recombinant Hirudine Plasmid for Thrombus Targeting Therapy.

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Novel Strategy of Gene Delivery System Based on Dendrimer Loaded Recombinant Hirudine Plasmid for Thrombus Targeting Therapy.