MANNOSE EXPLORATION AS A LIGAND FOR TARGETED THERAPEUTIC PROTEINS DELIVERY TO THE LIVER AND SPLEEN: AN EX VIVO STUDY

• Main Author: Giovanni Marsius, Agnes
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/74026
• Institution: Institut Teknologi Bandung

The ability of mannose to bind with its receptor could induce endocytosis and certain signaling pathways. Therefore, mannose could be potentially used as ligand for targeted-drug delivery system. Nowadays, researchs related to drug activity are limited to in vitro studies that can not describe the complexity of intercullar communication and in vivo studies that require enormous number of animal subjects. In this study, Precision Cut Tissue Slices (PCTS) method was developed as an ex vivo study that connected in vitro and in vivo studies. The process of tissue slicing and incubation was conducted to produce viable tissue. Tissue viability was measured by the content of ATP per protein and by trypan blue staining resulting rat liver and spleen tissue that remained viable for 24 hours of incubation with optimal viability at 2 hours of incubation. Staining with hematoxylin-eosin showed cell integrity in intact rat’s liver and spleen tissue. Assay related to the delivery of therapeutic protein using mannose as ligand was carried out by immunohistochemistry method. The mannose-conjugated Abmb protein could bind to the mannose receptor showed by the fluorescence intensity that dropped to 80%. Modeling of steatosis rat was also successfully conducted by high-fat food diet for 7 days and administration of ethanol 5 g/kg body weight intragastrically. The expression of mannose receptor increased in the liver of steatosis rats by up to 40%. Therefore, it could be potentially used as drug-delivery target, mainly for liver steatosis and inflammatory diseases.