DEVELOPMENT OF MITOCHONDRIA-TARGETED ALPHA-MANGOSTIN FORMULATION AND EVALUATION OF IN VITRO ANTIOXIDANT POTENTIAL

• Main Author: Adisty Zafira, Wina
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/85424
• Institution: Institut Teknologi Bandung

Mitochondria are organelles that served as the primary energy producers in cells. They are major contributors to reactive oxygen species (ROS), generating 90% of the total ROS. Excessive ROS could lead to oxidative stress and mitochondrial damage, which were involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s. Oxidative stress was characterized by the excessive production of ROS, which could cause mutations in mitochondrial DNA and damage the mitochondrial respiratory chain. Therefore, antioxidants specifically targeting mitochondria under oxidative stress were required. One compound with potential antioxidant properties was ?-Mangostin. The mechanism of action of ?-Mangostin as an antioxidant was associated with the modulation of antioxidant enzymes and a reduction in oxidative damage. This study aimed to develop mitochondria-targeted ?-Mangostin using liposomes modified with dequalinium (lipoDQ) and to evaluate its potential as an antioxidant. A comparison of the ratio between the phospholipid components, namely 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE) and cholesterol, was conducted. LipoDQ was prepared using a thin-film hydration method and sonication to reduce its size. Experimental results showed that particle size decreased and encapsulation efficiency (EE%) increased with a reduction in cholesterol concentration. The selected lipoDQ formula consisted of DOPE at 2.75 mM, ?-Mangostin at 0.275 mM, and dequalinium (DQA) at 1.375 mM. The lipoDQ had a particle size of 153.9 ± 9.04 nm, a polydispersity index (PDI) of 0.22 ± 0.01, an EE% of 75.56 ± 5.20%, and a zeta potential of +9.86 ± 1.51 mV. This zeta potential indicated successful incorporation of DQA into the liposomes and potential for increased lipoDQ accumulation in mitochondria. Based on stability tests, lipoDQ ?-Mangostin remained stable for 6 days of storage at 2 - 8°C. Antioxidant activity tests showed that ?-Mangostin encapsulated in lipoDQ had enhanced antioxidant activity with an IC50 of 67.53 ?g/mL, compared to the IC50 of 1699.12 ?g/mL for the ?-Mangostin solution. These results indicated that lipoDQ ?-Mangostin had potential as a mitochondria-targeted antioxidant agent.