Cardiovascular Drug Liposome

Cardiovascular disease, also known as circulatory system disease, is a disease with high human mortality. Approximately 17 million people die from cardiovascular disease worldwide each year. Cardiovascular and cerebrovascular diseases mostly occur after the age of 40. There are more men than women, and more mental workers than manual workers. The average prevalence is about 6.49%, and the prevalence increases with age. Affected by the high-fat, fast-paced, and high-stress lifestyle, the prevalence of cardiovascular and cerebrovascular diseases is increasing year by year, and the age of illness tends to be younger. Cardiovascular disease has become a major global medical problem.
According to the mechanism of action, drugs for the treatment of cardiovascular diseases can be divided into angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor antagonists (ARB), β-blockers, nitrates, diuretics, α- blockers, cardiotonic drugs and digitalis, lipid regulating drugs, antiarrhythmic drugs, calcium channel blockers, myocardial nutrition drugs; according to the disease can be divided into lowering blood pressure drugs, coronary heart disease drugs, and cardiac insufficiency drugs , Anticoagulant and antithrombotic drugs. Drug therapy is currently the most important and preferred method for the treatment of cardiovascular diseases, but most of the drugs lack tissue specificity and lesion site targeting. The amount of drugs is large, and some can cause toxic side effects. Therefore, the efficacy of drugs is not significant, and new types of drugs are urgently needed.

New Cardiovascular Drug Liposome
Thrombus Targeting Liposome
Cardiovascular disease is large-partly caused by blood clots. Thrombolytic drugs such as urokinase are used in large amounts, lack targeting and have a short action time. Targeted therapy is necessary for thrombotic diseases. Prostaglandin Er liposomes (Lipo-PGE) can significantly inhibit ADP-induced thrombosis and subsequent microcirculation vascular damage. Compared with ordinary prostaglandin E (PCE) preparations, the effect is significantly enhanced. The reperfusion time Lipo-PGEi group is PGE 1/4. In addition, using Lipo-PGEi after thrombosis is more effective than using Lipo-PGEi before thrombosis, indicating that liposomes can effectively target drugs to thrombus. Synthesize the specific ligand H-Arg-Gly-Asp-SeOH (RGDs) targeting thrombus, which is coupled with Distearoyl-phosphatidylethanolamine-polyethylene glycol 3500-carboxyl group and inserted into the liposome bilayer membrane, and then the thrombus-targeted urokinase liposome was obtained. The thrombolytic effect in vivo was investigated on the rat common carotid artery thrombosis model. The weight of thrombus in the free urokinase group was almost unchanged; the weight of the thrombus in the liposome urokinase group was slightly reduced but there was no significant difference. The weight of the thrombus in the thrombus-targeted urokinase liposome group was significantly reduced, and the dosage was reduced to 1/5, indicating Blood-targeted urine microenzyme liposome has obvious targeted thrombolytic effect.

Myocardial Targeting Liposome
Three factors should be considered for cardio-cerebrovascular targeting liposomes: ①Find specific receptors on the cardio-cerebrovascular; ②Attach ligands that specifically bind to the receptors on the surface of the liposomes, ③prevent the liposomes from being meshed The endothelial system is removed. The β receptor ligand allylolol is mixed into human liposome membrane to make myocardial targeted liposomes, which are mainly distributed in tissues and organs rich in β receptors such as heart and lung. The liposome can treat myocardial necrosis after encapsulating reduced glutathione and reduce the dosage of drugs. Myocardial ischemia can lead to the death of cardiomyocytes, and antibodies against intracellular antigens can distinguish live cells from dead cells, undamaged cell membranes and damaged cell membranes. Myosin in the heart will not be taken away due to cell rupture and can be used as a target for antigen-specific binding during myocardial ischemia. For example, liposomes modified with anti-myosin antibodies can actively target the ischemic myocardium Location. The interaction mechanism between cardiomyocytes and liposomes is not very clear. Cardiomyocytes may adsorb liposomes and interact with liposomes through membrane lipid exchange, fusion, and endocytosis. The liposomes deliver drugs into the cardiomyocytes. Experiments have proved that the isolated rat cardiomyocytes take up liposomes in a variety of ways, and the mode of action mainly depends on the physical state of the liposomes (phase transition temperature and electrical properties), rather than the lipid composition. For positively charged The uptake of liposomes is much greater than that of negatively charged liposomes. The gel state liposomes ingested through endocytosis and adsorption are higher than the liquid crystal state liposomes, and the liquid crystal neutral liposomes ingested are higher than the liquid crystal state charged liposomes. The uptake of liposomes, especially positively charged liposomes, by ischemic myocardium tissue increases significantly. The order of intake is: ischemia-reperfusion zone, infarct marginal zone, non-ischemic zone and infarct zone. The mechanism It is related to K and Ca disorders in damaged tissues and membrane lipid peroxidation. Therefore, liposomes are an ideal carrier and are used to carry drugs. Further animal model analysis found, liposomes were significantly increased in the heart and lungs of rats with isoprenaline myocardial ischemia, and the uptake of liposomes in the duodenum, jejunum, ileum, and heart of rats with superior mesenteric artery occlusion shock increased significantly. In addition, liposomes are more distributed in the liver and lungs, and these organs themselves are the main target organs of shock. What is more significant is that the uptake of liposomes by the small intestine tissue after ischemia doubles, so liposomes are used as drug carriers for treatment of myocardial ischemia and anti-shock has good prospects.