Simvastatin-loaded nanostructured lipid carriers attenuate the atherogenic risk of erythrocytes in hyperlipidemic rats.
This study aimed to investigate the effect of simvastatin (SV) loaded nanostructured lipid carriers (SV loaded NLCs) on atherogenic index (AI), erythrocytes membrane lipid and antioxidant/pro-oxidant status in hyperlipidemic rats. SV loaded NLCs were successfully prepared with desired nano-particles size, spherical shape, high encapsulation efficiency (EE %) and sustained SV release. The results of biological studies revealed that administration of SV loaded NLCs to rats increased SV bioavailability compared to SV suspension. Intraperitoneal injection of tyloxapol as hyperlipidemic agent induces a significant increase of plasma AI, uric acid, lipid peroxidation and protein oxidation. While, plasma total antioxidant capacity and paraoxonase-1 activity were significantly decreased. Moreover, tyloxapol induced-hyperlipidemia increases erythrocyte's membrane cholesterol and deteriorates erythrocyte's antioxidant enzyme activity, GSH/GSSG ratio and NO level However, the propagation of erythrocyte's pro-oxidant activity and hemolysis was observed. On the contrast, the treatment of these rats with SV loaded NLCs improved the measured parameters compared to rats received SV suspension and hyperlipidemic rats. The predominant effect of SV loaded NLCs may be attributed to the enhancement of absorption, prolonged duration and improvement of bioavailability of SV. Accordingly, SV loaded NLCs showed advantageous effects on the blood lipid levels and atherogenic risk of erythrocytes in hyperlipidemic conditions compared to SV suspension.
Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia; Department of Biochemistry, College of Pharmacy, Al-Azhar University (Boys), Nasr City, Cairo, Egypt.
Gamaleldin I
GI
Harisa
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia; Nanomedicine unit (NMU-KSU), College of Pharmacy, King Saud University, Saudi Arabia.
Abdullah H
AH
Alomrani
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. Electronic address: mbadran75@gmail.com.
Mohamed M
MM
Badran
D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D065546:Drug Liberation; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D012306:Risk; D019821:Simvastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D004337:Drug Carriers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D019821:Simvastatin
Dyslipidemia; Erythrocytes; Nanostructured lipid carriers; Oxidative stress; Rats; Simvastatin