PENGEMBANGAN SISTEM PENGHANTARAN BERTARGET INTERFERON ALFA 2B KE HATI DENGAN METODE GALAKTOSILASI
Interferon-alpha2b (IFNu2b), which possesses antiviral, immunomodulatory, and anti proliferation activity, is a therapeutic protein used for chronic infections caused by viral hepatitis. However, IFN-u2b has many limitations such as short biological half life and rapid elimination which requires fre...
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| Format: | Theses |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/71690 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Interferon-alpha2b (IFNu2b), which possesses antiviral, immunomodulatory, and anti proliferation activity, is a therapeutic protein used for chronic infections caused by viral hepatitis. However, IFN-u2b has many limitations such as short biological half life and rapid elimination which requires frequent administration, leading to the development of adverse side effects. Therefore, the liver targeted delivery system need to be developed to improve the accumulation in the liver subsequently reducing the dose. In this study, liver targeted system of IFNu2b has been developed through asialoglycoprotein receptor (ASGP-R). Galactose is used as the homing device.
IFNu2b was obtained from synthetic IFNu2b gene produced in E. coli BL21. Purification was done using affinity chromatography. IFNu2b was conjugated with galactose according to amination reduction method using sodium cyanoborohydride. Characterization of galactosylated interferon (Gal-IFNu2b) was performed using SDS PAGE, and in vitro activity assay was done using MTT assay in HepG2 cell. Biodistribution and pharmacokinetic profiles were studied in animal models using radiolabelling with technetium-99m.
Conjugate of Gal-IFNu2b was obtained with protein:galactose ratio of 1:8. The in vitro activity was not decreased shown by MTT assay ill HepG2 cells. Gal-IFNu2b was mainly distributed to the blood, kidney, and liver. Meanwhile, significant reduction of Gal-IFN-u2b was observed in blood and kidney (p<0.05) between 10 and 30 minutes after injection, while there was no significant reduction in liver. Phamacokinetic data showed that elimination half time of Gal-IFNu2b was 60.88 ± 24.98 minutes, and the distribution half life was 4.96 ± 2.26 minutes.
Gal-IFNu2b conjugate has been succesfully developed without any loose in the biological activity. The biodistribution profile showed that the conjugate was not
highly accumulated in liver but remained present in the liver up to 30 minutes after injection.
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