ReviewPost screenApplication of nanotechnology to improve the therapeutic benefits of statins
Introduction
Cardiovascular disease is a major cause of death, worldwide. Hyperlipidemia is one of the most important risk factors in the development and progression of cardiovascular disease and is characterized by elevated plasma lipoproteins, including LDL-C and triglycerides (TGs) [1]. Statins are the most common medication prescribed to lower plasma lipids and decrease the risk of developing cardiovascular disease. Statins primarily target LDL-C and the degree to which statins lower LDL-C generally ranges from ∼10% to ∼40% [2].
However, statins have low oral bioavailability primarily because of their limited aqueous solubility and some have a considerable molecular weight. Additionally, significant numbers of patients develop drug-related adverse effects. Improved bioavailability of statins has potential to reduce the adverse effects and toxicity associated with higher statin plasma concentrations [3], and efficient delivery systems may improve this bioavailability. Here, we summarize novel drug delivery systems and their therapeutic utility for statin delivery.
Section snippets
Properties of statins
Statins inhibit HMG-CoA reductase, thereby lowering elevated LDL-C and reducing the incidence of cardiovascular disease [4]. Statins also moderate the plasma concentrations of other lipids, including TG and high-density-lipoprotein cholesterol (HDL-C) [5].
Interactions between HMG-CoA and HMG-CoA reductase cause conversion of HMG-CoA to L-mevalonate, the rate-limiting step in cholesterol synthesis. Competitive inhibition of HMG-CoA reductase by statins reduces cholesterol synthesis in the
Absorption and bioavailability
Statins have recently been evaluated in the prevention of a variety of diseases, including osteoporosis, Alzheimer’s disease, stroke, cardiac diseases, and diabetes, as well as offering benefit post organ transplantation [18]. Statins have potential neuroprotective and neurorestorative effects on cerebrovascular disease, such as ischemic stroke, and in neurodegenerative diseases such as Parkinson’s disease. The beneficial effect appears to be mediated through a reduction in cholesterol level
Concluding remarks
Nanotechnology provides advantages for the delivery of statins, most importantly in oral bioavailability. At least two mechanisms should be considered to enhance the oral bioavailability of statins: (i) increasing their dissolution in the gastrointestinal tract; and (ii) reducing and/or eliminating first-pass metabolism following oral absorption, which can prevent some statins from attaining desired systemic concentrations.
Given that oral administration of statins is preferable, improving
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