ANTIHYPERCHOLESTEROLEMIA ACTIVITY STUDY OF SIMVASTATIN WITH LIPID NANOPARTICLES (LNP) AS DRUG DELIVERY SYSTEM IN HEPG2 CELLS

• Main Author: Rula Akifah, Latisha
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78419
• Institution: Institut Teknologi Bandung

High levels of Low Density Lipoprotein (LDL) cholesterol in plasma will cause thickening and sticking of LDL cholesterol to the plasma wall and cause plaque which can lead to atherosclerosis. Hypercholesterolemia is the biggest risk factor for atherosclerosis where there is an increase in cholesterol levels in the blood, especially LDL cholesterol. Statins are the first-line therapy for lowering LDL cholesterol by inhibiting HMG-CoA reductase, and mevalonate will not form, leading to interferes with cholesterol biosynthesis in the Endoplasmic Reticulum (ER). One of the statin drugs is simvastatin which is effective in reducing LDL cholesterol levels. However, the bioavailability of simvastatin is only 5% and undergoes first-pass metabolism in the liver. Because of the poor bioavailability of simvastatin, the use of Lipid Nanoparticles (LNP) is needed to increase the bioavailability of simvastatin via the intravenous route of administration with targeted drug delivery to ER. In this study, cell viability was tested on HepG2 cells using MTT (3-[4,5- dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) reagent to determine the safe concentration of simvastatin LNP and the concentration were obtained at 3, 6, 9 ?g/mL is the safe concentrations of LNP simvastatin with the cell viability are >70% based on research results. These concentrations were tested for their antihypercholesterolemic activity on the HepG2 cell line which is a hepatocyte. The aim of this study was to determine the safe and effective concentration of simvastatin LNP in lowering LDL cholesterol levels by in vitro testing on HepG2 cells. Antihypercholesterolemic activity testing was carried out by making three test groups, the first is the HepG2 cell group without treatment, the second is the HepG2 cell group in hypercholesterolemic conditions with the addition of 100, 200, 400, 800 ?g/mL LDL cholesterol extracellularly, and the last group is the HepG2 cells in hypercholesterolemic condition then given treatment by 3, 6, 9 ?g/mL LNP simvastatin. Based on the research results, a concentration of 6 ?g/mL was obtained which was effective and safe in reducing LDL cholesterol levels with cell viability of 79.2% and succeeded in reducing cholesterol levels significantly (p=0.005) when compared with LDL cholesterol levels in HepG2 cells with hypercholesterolemic conditions.