A nano-enabled biotinylated anti-LDL theranostic system to modulate systemic LDL cholesterol

Cardiovascular diseases (CVDs) remain one of the leading causes of death with an estimated 17.9 million lives lost each year. Circulating high levels of low-density lipoproteins (LDL), are susceptible to various modifications such as oxidation and glycosylation (diabetics). This leads to development of atherosclerosis, which can impair quality of life and death. There is a growing need for detection and subsequent treatment of high LDL cholesterol, which could be achieved through design of a system for detection of LDL with subsequent drug release for disease management. Fenofibrate-loaded solid lipid nanoparticles (SLNs) were synthesized and coated with anti-oxidized LDL antibodies to form anti-LDL SLN. The nanoparticles were delivered via an osmotic pump delivery device implanted on the jugular vein of Large White pigs as an anti-LDL theranostic system, referred to as an Intra-Vascular Implantable Sensor and Drug Delivery Device (IVISDDD), for modulation of systemic LDL cholesterol levels. Modulatory fenofibrate release was observed from the IVISDDD following in vivo analysis in response to anti-LDL SLN-LDL complex uptake and degradation. This notably contributed to a 29.9% reduction in total cholesterol via a 37.4% reduction in LDL levels, and an increase in HDL levels. The observed effect on cholesterol levels indicated that the device could be employed for detection of circulating biomarkers and delivery of lipophilic drugs in CVDs.