BIOCOMPATIBILITY STUDY OF LEVAN AS NANOCARRIER MATERIAL FOR ORAL INSULIN WITH IN SILICO METHOD

• Main Author: Tong, Michael
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/62712
• Institution: Institut Teknologi Bandung

Oral insulin has long been an anticipated alternative for diabetic patient for its practicality and ease to use, compared to the current subcutaneous insulin injection. However, the biggest obstacle of low pH in gastroinestinal system still need to be overcome for further oral insulin development. A compatible and effective carrier for oral insulin is also needed for high insulin bioavailbility to become an effective diabetic drug. Levan, an inulin like biopolymer, is a strong candidate for insulin carrier due to properties such as amphiphilic polymer, good biocompability and hyperglycemic inhibitor. Molecular dynamics simulation is used as the approach to test the biocompability of levan as an insulin carrier. The simulation is run at constant temperature and pressure for 200 ns with integration time of 2 fs. The non- bonding potential energy is measured at 10 Å cut off with the temperature and pressure maintain at 400 K and 1 bar. To simulate the acid condition at gastointestinal tract, the simulation is run with the pH variation of 1 and 7 as the control. Visualization result with VMD for the insulin (PDB ID: 5ENA) – levan system showed that levan is not always surrounding the insulin for the whole simulation. RDF (Radial distribution function) analysis showed the levan population whereabout is more pronounce at pH 7 compared to pH 1 condition with the same 15 Å distance from insulin protein. Whenever insulin is not protected by levan, its secondary structure is damaged. Secondary structure analysis result point out that the protection of levan is better seen at pH 7 condition rather then pH 1 condition. The capability of levan for insulin protection to some extent is evaluated with RMSD (root-mean-square deviation) value calculation. Ther result between RMSD value of insulin with levan and without levan at pH 7 is decreasing from 7,79 Å to 4,23 Å after 200 ns. Although at pH 1, there have been an increase RMSD number from 2,56 Å to 3,01 Å after introduction to levan. This result indicate the differing effect of levan between both pH condition. Further analysis to observe the protection effect of levan is to observe the fluctuation of insulin residues throu RMSF (root-mean-square fluctuation) analysis. This result demonstrate the effect of levan surrounding the insulin can dampen the insulin residues fluctuation. From above information, it can be concluded that levan is a biocompatible material to be used as oral insulin carrier.