INULIN PRODUCTION FROM HALOPHILE BACTERIA SALINIVIBRIO COSTICOLA GM01 FOR DEVELOPING ORAL INSULIN DELIVERY SYSTEM

• Main Author: Ramadhanna'il Rasjava, Achmad
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/67509
• Institution: Institut Teknologi Bandung

Diabetes mellitus is a chronic long-term condition that occurs when the body cannot produce enough insulin or cannot use the insulin effectively. The main categories of diabetes are type 1 and type 2 diabetes. Subcutaneous insulin injections are commonly used in the daily management of diabetes mellitus. But it is difficult to meet patient compliance because of the discomfort associated with administering insulin. Oral insulin administration offers advantages such as reduced risk of hypoglycemia, greater adherence, and reduced pain. However, certain physiological barriers must be overcome for oral insulin delivery. Several previous studies have shown that insulin protection with inulin can minimize these physiological barriers. Several previous studies have shown that insulin protection with inulin can minimize these physiological barriers effects. Inulin applications have been widely studied include its role in protein stabilization and modified drug delivery for increased dissolution rate and drug targeting. Over the past decade, increasing efforts have been made in the application of nanoparticles as oral insulin delivery agents. Drug delivery system as nanoparticles has the largest surface area:volume ratio of all dosage forms so it can affect the properties of the particles that will affect the bioavailability of the drug it carries. Various natural polymer nanoparticles, synthetic polymer nanoparticles and inorganic nanoparticles have been investigated. In this study, an exopolysaccharide-based insulin carrier nanoparticle produced by the halophilic bacteria Salinivibrio costicola GM01 was developed as a vessel for oral insulin. The halophilic bacteria Salinivibrio costicola GM01 was able to produce inulin type exopolysaccharide with a production capacity of 89,43 ± 13,54 mg/50 mL of production media. Modification of inulin through acetylation was successfully carried out, indicated by the appearance of a new peak in the FTIR spectrum at a wave number of ~1.720 cm-1. Optimization results using RSM method showed the optimum conditions for the synthesize of acetylated insulin-inulin nanoparticles using 1,029 mL of acetic anhydride, 52,83 mg of acetylated inulin and stirring speed of 17.815,68 rpm. The size of acetylated inulin-insulin nanoparticles has a fairly narrow distribution, which is 354,51 ± 38,83 nm. Statistical test with 95% confidence level was used to see the significance of the data. Inulin acetylation can increase insulin encapsulation efficiency up to 7,46% and loading capacity up to 2,21%. Encapsulation stability test showed that inulin acetylation was able to improve insulin encapsulation performance compared to inulin without acetylation, indicated by ??H‡ values of 53,34 ± 1,97 kcal/mol and 48,53 ± 1,33 kcal/mol at pH 1,0 and 7,0 at 37°C. Analysis of the stability of the secondary and tertiary structures of insulin using circular dichroism and spectrofluorometer showed that acetylation was able to improve the conformational protection performance of insulin compared to inulin without acetylation, indicated by ??H‡ values of 2,28 ± 0,03 kcal/mol; 0,80 ± 0,16 kcal/mol; 16,70 ± 0,46 kcal/mol; -0,63 ± 0,52 kcal/mol at pH 1,0 and 7,0 at 37°C. The results showed that acetylation could improve the performance of inulin and its potential as an oral insulin delivery agent.