FOLIC ACID AND BOVINE SERUM ALBUMIN (BSA) CONJUGATE AS DUAL TARGETING NANOPARTICLE CHITOSAN CONTAINING MANGOSTIN IN DRUG DELIVERY SYSTEM FOR BREAST CANCER CELL LINE (MCF-7)

• Main Author: Kamilatussaniah
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/46988
• Institution: Institut Teknologi Bandung

Cancer is a complex disease caused by uncontrol cell division which caused by proto-oncogene and tumor suppressor gene. The study and development an effective and efficient cancer therapy method is still ongoing. One of therapy method currently being used is by using nanotechnology and the use of anticancer bioactive substance. Cancer cells especially breast cancer cells are known to highly express several receptor and protein molecule such as folic acid receptor as high affinity to folic acid and Secreted Protein Acidic and Rich in Cystein (SPARC) as high affinity to albumin. These two molecules could potentially used as specific targets for anticancer drugs and therapy. Bioactive substance, such ?-Mangostin. ?-Mangostin is known to induce apoptosis and inhibit cell proliferation. However, ?-Mangostin has a very low solubility, therefore encapsulation of ?-Mangostin using nanoparticle is needed. The objective of this research is to conjugate and BSA containing ?-Mangostin. Chitosan nanoparticle and determine its cytotoxicity to breast cancer cell (MCF-7). In this research, chitosan nanoparticle has made using ionic gelation method. The dual targeting of BSA and folic acid is expected to increase the nanoparticle intracellular uptake, hence increased cytotoxicity of ?-Mangostin to breast cancer cell (MCF-7). The results of this research showed that chitosan nanoparticle could be synthesized by ionic gelation. The size and zeta potential of nanopaticle were measured using Particle Size Analyzer (PSA). Nanoparticle that has been made are chitosan nanoparticle containing ?-Mangostin conjugated with or without folic acid and BSA (NP-KFBM & NP-KFB), ?-Mangostin-containing chitosan nanoparticle conjugated by folic acid (NF-KFM & NP-KF), ?-Mangostin-containing chitosan nanoparticle conjugated by BSA (NP-KBM & NP-KB), and ?-Mangostin-containing chitosan nanoparticle & only chitosan nanoparticle (NP-KM & NP-K) showed that the size of ?-Mangostin-containing chitosan are 299,3 nm, 227,7 nm, 207,3 nm and 154,1 nm respectively. The zeta potential value of NP-KFBM, NP-KFM, NP-KBM and NP-KM were11 mV, 19,9 mV, 14 mV, and 25 mV respectively. FTIR analysis showed that there were amine groups ( NH2), hydroxyl groups (OH) and amide I groups. Scanning electron microscope (SEM) analysis showed that the nanoparticle morphology was spherical. The encapsulation effieciency of ?-Mangostin in nanoparticle was 69% (NP-KFBM), 73,341% (NP-KFM) and 69,5% (NP-KBM). Drug release etudy was conducted at pH 4.8 and 7.4. The result showed ?-Mangostin is released at pH 4.8. The drug release absorbance at pH 4.8 is higher than at pH 7.4. Nanoparticle toxicity test towards MCF-7 shows that there is a significant difference of IC50 value of uncapsulated ?-Mangostin and ?-Mangostin is capsulated in chitosan nanoparticle with conjugates. The IC50 value of NP-KFBM, NP-KFM, NP-KBM and NP-KM is 1,17 ± 0,25 ?g/ml (2,85 ?M), 1,44 ± 0,08 ?g/ml (3,5 ?M), 1,35 ± 0,31 ?g/ml(3,28 ?M), and 1,86 ± 0,32 ?g/ml (4,53 ?M). The IC50 value of uncapsulated ?-Mangostin is 4,06 ± 0,48 ?g/ml (9,89 ?M). The result of nanoparticle internalization test by MCF-7 showed that NP-KFBM and NP-KBM start to be internalized at the 9th hour after treatment. In summary, folic acid and BSA have been conjugated successfully to nanoparticle containing ?-Mangostin. The nanoparticles have been synthesized and characterized. Mangostin encapsulated in has lower IC50 than free ?-Mangostin to MCF-7 cells.