FORMULATION AND CHARACTERIZATION OF NANOSTRUCTURED LIPID CARRIER (NLC) LOADED SIMVASTATIN AND CYTOTOXIC ACTIVITY AGAINST TRIPLE NEGATIVE BREAST CANCER (TNBC)

• Main Author: Zoe Immanuella, Marvel
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/85431
• Institution: Institut Teknologi Bandung

Triple Negative Breast Cancer (TNBC) is a type of breast cancer that does?’?have the hormone receptors estrogen, progesterone, and HER2. TNBC is known as the most aggressive subtype of breast cancer with a high recurrence rate, low cure rate, and low survival rate. Having absent of all three hormone receptors means therapy options for TNBC are more limited. In addition, many cases of chemoresistance in TNBC have been reported due to chemotherapy, which is the main therapy option for TNBC. For this reason, it is necessary to develop alternative therapies that are more effective, one of which is using the concept of drug repurposing combined with a drug delivery system. One potential drug candidate is simvastatin, a statin anti-hyperlipidemia drug. In this research, a simvastatin (Sim) delivery system using Nanostructured Lipid Carrier (NLC) has been developed and cytotoxic activity against TNBC has been tested. The research aimed to determine the optimal formula and manufacturing process for NLC-Sim, test the characteristics of NLC-Sim, test the stability of NLC-Sim, and test the cytotoxic activity of NLC-Sim. The research began with a formula optimization process followed by characterization and stability testing of NLC-Sim. The optimal formula was then tested for cytotoxic activity against 4T1 cells which are model of TNBC. The results of formula optimization have obtained an optimal formula with beeswax and virgin coconut oil (VCO) as solid lipid and liquid lipid components with a total concentration of 4% and a ratio of 3:1. The surfactant combination has been obtained was Tween 80 and PEG 400 with a total concentration of 5% and a ratio of 4:1. Based on process optimization, an optimal sonication process has been obtained which is a combination of two sonication stages using bath sonicator and probe sonicator. The optimal NLC-Sim had a particle size of 192.10 ± 11.73 nm, a polydispersity index of 0.25 ± 0.02, a zeta potential of -8.67 ± 2.41 mV, and an encapsulation efficiency of 99.11 ±0.25%. NLC-Sim has shown adequate stability when stored at 2-8 °C for 14 days. The results of the cytotoxic test on 4T1 cells showed that NLC-Sim had a better effect than NLC blank and simvastatin solution, with an IC50 value of 80.84 ± 11.62 µM. These results have indicated that simvastatin delivery system using NLC had potential as an alternative therapy for TNBC.