Nanoparticle-mediated drug delivery system for atherosclerotic cardiovascular disease

Abstract

Administration of drugs and other therapeutic agents has been the central strategy of contemporary medicine for cardiovascular disease. The use of drug delivery systems (DDS) includes micelles, liposomes, polymeric nanoparticles, dendrimers, carbon nanotubes, and crystalline metals. Nano-DDS modify in vivo drug kinetics, depending on (patho)physiological mechanisms such as retard excretion, vascular permeability, and incorporation by mononuclear phagocyte systems, which constitute the 'passive-targeting' property of nano-DDS. These properties of nano-DDS are applicable to inflammatory diseases including atherosclerosis. Atherosclerotic plaque destabilization and rupture account for the majority of acute myocardial infarction, for which inflammatory monocytes and macrophages play critical roles. In our experience, polymeric nanoparticles have been delivered to inflammatory monocytes and macrophages in an atherosclerotic mouse model. Nano-DDS loaded with pioglitazone reduced Ly6C inflammatory monocytes and increased Ly6C non-inflammatory monocytes in the peripheral blood, and induced M2 macrophage-associated genes in the aorta. Pioglitazone-nanoparticles finally stabilized atherosclerotic plaques assessed by a decrease in the number of buried fibrous caps in the plaque. Application of nano-DDS is a unique and promising approach to prevent life-threatening cardiovascular events including acute myocardial infarction by regulating inflammation in the cardiovascular system.

Effects of nanoparticle‑mediated delivery of pitavastatin on atherosclerotic plaques in ApoE‑knockout mice and THP‑1‑derived macrophages

“…These studies have confirmed that P-NP at a 100 to 840-fold lower single dose appears to be as effective as a cumulative systemic dose of pitavastatin (6,7). The properties of NP-DDS may be the result of two major mechanisms: i) Recognition and incorporation by the mononuclear phagocyte system (monocytes, macrophages and neutrophils), which may affect the blood circulation time and tissue/cell distribution of drugs delivered by the NP-DDS; and ii) enhanced vascular permeability contributing to enhanced drug delivery for atherosclerotic arterial walls and macrophages (28). In the present study, FITC-NP was still detected in the atherosclerotic plaque 7 days after a single administration, leading to the conclusion that FITC-NP may be recognized and incorporated by macrophages.…”

<p>Multifunctional PLGA-based nanoparticles as a controlled release drug delivery system for antioxidant and anticoagulant therapy</p>

“…NPs are attractive nanocarriers with therapeutic applications in the early detection of biomarkers and the treatment of vascular diseases. [19][20][21][22] Surface modification, such as by the layer-bylayer (LbL) technique, can be used to control the half-life of the encapsulated drug in the system. The fabrication of LbL NPs by alternately coating oppositely charged polymers or biomolecules on various colloids can produce a promising delivery system with high loading efficiency, easy functionalization, tunable multifunctionality, and responsiveness to stimuli.…”

Application of the Nano-Drug Delivery System in Treatment of Cardiovascular Diseases

“…NDDSs refer to material in which at least one dimension is in the range of nanometer scale (1-100 nm) or composed of them as basic units in three-dimensional space (Cooke and Atkins, 2016;Zhou et al, 2018). As an effective means to optimize the drug delivery, NDDSs have become a research hotspot in the field of pharmacy and modern biomedicine (Matoba et al, 2017). The investigation of NDDSs has been for more than 40 years, creating a mass of nano-drug carriers.…”