Towards the application of alginate cell microencapsulation technologies to treat brain tumors. (Doctoral thesis)

Successful treatment of brain tumors is one of the most challenging tasks in oncology. Despite of advanced treatment options of debulking tumor mass by surgery, radiation, and chemotherapy; tumor reoccurrence is inevitable with overall survival rates of less than 15 months. Systemic brain tumor chemotherapy is seriously hampered by presence of blood brain barrier (BBB) which limits drug delivery to the brain. Encapsulating drugs in nanocarriers like liposomes, micelle, and nanoparticles have shown promising result. However these nanocarriers are suffering from major drawbacks such as low encapsulation efficacy, limited stability, difficult synthesis of polymer and high cost of preparation. Circumventing the BBB by local delivery using alginate cell encapsulation is a promising way to treat brain tumor. In this thesis we focus on alginate cell encapsulation technology as an alternative approach to treat brain tumors. Recent data from pre-clinical work indicate that this approach merits consideration for future clinical translation for brain tumor treatment. However several crucial issues like mechanical stability of capsules, lab-to-lab variations in coating, and more importantly protrusion of cells are obstacles hampering clinical application. These issues have been addressed step by step in this thesis with the aim for successful translation of this approach into clinical application. The novel encapsulation overcomes challenges in traditional encapsulation system and merits for considering the approach in clinical application.
AB - Successful treatment of brain tumors is one of the most challenging tasks in oncology. Despite of advanced treatment options of debulking tumor mass by surgery, radiation, and chemotherapy; tumor reoccurrence is inevitable with overall survival rates of less than 15 months. Systemic brain tumor chemotherapy is seriously hampered by presence of blood brain barrier (BBB) which limits drug delivery to the brain. Encapsulating drugs in nanocarriers like liposomes, micelle, and nanoparticles have shown promising result. However these nanocarriers are suffering from major drawbacks such as low encapsulation efficacy, limited stability, difficult synthesis of polymer and high cost of preparation. Circumventing the BBB by local delivery using alginate cell encapsulation is a promising way to treat brain tumor. In this thesis we focus on alginate cell encapsulation technology as an alternative approach to treat brain tumors. Recent data from pre-clinical work indicate that this approach merits consideration for future clinical translation for brain tumor treatment. However several crucial issues like mechanical stability of capsules, lab-to-lab variations in coating, and more importantly protrusion of cells are obstacles hampering clinical application. These issues have been addressed step by step in this thesis with the aim for successful translation of this approach into clinical application. The novel encapsulation overcomes challenges in traditional encapsulation system and merits for considering the approach in clinical application.