The blood-brain barrier (BBB) continues to represent one of the most significant challenges for successful drug delivery in the treatment of neurological disease. Modulation of structure-activity relationship profiles in drug design have provided only limited clinical success and alternative therapeutic systems are therefore required. In recent years, locally permeabilizing the blood-brain barrier by focused ultrasound has shown considerable promise, with several first-in-human clinical trials reporting successful outcomes for patients with glioblastoma.
A further challenge, however, is posed by metastatic tumours. These represent a leading cause of mortality in cancer patients and can only be successfully treated when they are below a critical size. Unfortunately, both detection and treatment by chemotherapy are severely limited by the BBB. Under the EPSRC funded Oxford Centre for Drug Delivery Devices in collaboration with Prof. Nicola Sibson’s team in the Department of Oncology we have developed targeted micro and nanoparticles that bind to the sites of tumours enabling them to be detected and treated at an early stage using low intensity ultrasound.
As part of this project we have also developed a new microbubble formulation that increases drug delivery efficiency by locally fluidising cell membranes; producing a 5-fold increase in intracellular drug uptake in vitro and a 2-fold increase in delivery across the blood brain barrier in vivo. This allows us to minimise the ultrasound intensities required and hence the risk of off-target effects.