Nanoparticles as agents for targeted delivery in the treatment of vascular pathologies. Research result: pharmacology and clinical pharmacology

Abstract

Inflammation in the pathogenesis of cardiovascular diseases. Inflammation is the cornerstone of CVD. Systemic inflammation can lead to activation of the endothelium characterized by increased expression of endothelial adhesion molecules and chemokines (e.g., vascular adhesion molecules [VCAM] and monocyte chemotactic protein [MCP-1]), as well as reduced expression of anti-atherogenic molecules. Statins are the most effective treatment for hyperlipidemia and remain the gold standard for the treatment of vascular inflammation and CVD.

New strategies and approaches to targeted delivery of drugs. These approaches are mainly based on two main aspects: 1) pharmaceutical composition which allows to encapsulate therapeutic agents; 2) surface functionalization with the help of a target agent (i.e., antibodies and small molecules) for drug delivery to endothelium. Nanostructured mesoporous silicon vectors (MSV) charged with 10-nm polymer micelles are used as a tool for the treatment of chronic heart failure. Another approach is the development of carriers that are analogues of natural adhesion molecules (CAM) or selectin ligands.

The strategy of treatment of cardiovascular diseases with preparations based on nanoparticles. For the visualization of atherosclerotic plaques, nanoparticles conjugated with indium (111In) based on antibodies bound to LOX-1 receptors of low density were used in mice.

New ideas and opportunities for drug development. 1) development of carrier-based microorganisms (such as bacteria or viruses), or cells (e.g. leukocytes, erythrocytes, platelets and stem cells); 2) development of nanoparticles with analogues of biologically active molecules that bind to cell membranes. Additional approaches include lacto-glycolic acid polymers (PLGA). Another approach to delivering drugs to the endothelium is to create a nanocapsule based on high molecular weight polymers with a nucleus containing a drug substance. This may allow switching from a three-compartment pharmacokinetic model to a one-cell model.