Preparation and characterization of in situ gelling system containing meis protein inhibitor loaded albumin nanoparticles and iRGD peptide

Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by a stromal barrier in which fibrotic tissue surrounds the tumor. This barrier restricts access to tumor cells of chemotherapeutic agents administered to individuals with PDAC. Crossing the stromal barrier is critical to the success of the treatment. Albumin has great potential to overcome this barrier, with its ability to bind to SPARC proteins overexpressed in the PDAC tumor microenvironment. Another target point to overcome the stromal barrier is integrin receptors. The iRGD peptide binds to the integrin receptor in stromal cells, allowing therapeutic agents to be administered into the cell. MEIS proteins, which contribute to cancer formation by binding to DNA, cause resistance to chemotherapy as well as oncogenic activities. MEIS protein inhibitor suppresses tumor activity by binding to MEIS. In this master thesis, an in situ gelling system based on Poloxamer® 407/Chitosan designed for application to the pancreatic duct. MEIS inhibitor-2 loaded albumin nanoparticles and iRGD peptide were dispersed in the in situ gelling system. The physicochemical properties of the formulation and its activity on pancreatic cancer cells were evaluated in vitro.