The effect of atorvastatin loaded aptamer conjugated silica nanoparticles on anti-inflammatory signaling pathway in huvecs

In worldwide, cardiovascular diseases (CVD)are first causes of death and affecting millions of humans. Atherosclerosis is a type of chronic inflammatory disease that limits flowing of high oxygen contain blood to organs. Progress of atherosclerosis may result in heart attack and stroke. Drug therapy still is not available to date that directly target and suppress the molecular mechanisms of inflammation. In current clinical practice, only few therapies such as statin and aspirin are effectively diminishing the cardiovascular diseases such as atherosclerosis. However, only 30 to 40 percent of the patients give positive feedback to these treatment strategies. Therefore, it is important to develop the safe delivery of drug administration to the disease region. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors that prevent production of LDL inside liver. Besides to cholesterol reducing effect of statin, they have various pleiotropic effects in this way they act as vascular protective. This study aim was to evaluate therapeutic efficiency of atorvastatin loaded targeted and controlled release system compared to only atorvastatin via p-Akt/eNOS activation pathway in endothelial cells. For this reason, ICAM-1 specific Aptamer conjugated Atorvastatin encapsulated mesoporous silica nanoparticles (ICAM-1 APT-Atorv MCM41) was developed. HUVEC stimulated six hours with TNF-α for then incubated with Atorvastatin and ICAM-1 APT-Atorv MCM41 for 24 hours. mRNA expression of eNOS and protein levels of eNOS and p-Akt and were observed with RT-PCR and Western blot methods. This study results indicated that targeted delivery of atorvastatin increased eNOS and p-Akt (Ser473) expression level. In conclusion, ICAM-1 Aptamer conjugated atorvastatin encapsulated MCM-41 nanoparticle drug delivery system may provide new candidate approach for preventing atherosclerosis.