The Blood-Brain Barrier remains a challenge to cross, stunting the development of treatments for brain diseases. Some potential methods have been developed, including microbubble or osmotic diuretic-induced transient barrier disruption. However, they prove to be invasive or have some adverse side effects. The novel method we are developing is a noninvasive approach to cross the blood-brain barrier and deliver a payload of drugs. We propose that through changing the shape of a polymersome, a polymeric nano-vesicle, to create more surface area, a greater amount will be able to be taken up by the endothelial cells and thus be delivered to the brain. Up to this point, our lab has observed a shape change of polymersomes into prolates using one specific block-copolylmer. The shape change was driven by a salt gradient to create an osmotic pressure outside of the formed polymersome, bending the polymersome into a prolate. The research will continue by using increasing concentrations of salt gradients to discern whether we can further increase the surface area of the prolate. We will also research whether we can turn other materials, that have beneficial applications in treatment, into prolates.

Completion of this project will help advance the entire field of drug delivery, by providing a novel way to delivery drugs to the brain. It would prove to be less invasive than methods currently in use, including the use of osmotic diuretics to temporarily open the blood-brain barrier which can put the patient at risk of blood borne pathogens entering the brain. The advancement in research would help change the lives of millions of people suffering from brain illnesses. Not only that, but it would help advance medical science to overcome the blood-brain barrier using a tunable and widely applicable method. Although this proposal only explores the use of biodegradable polyesters, polymersomes can be formed by polymers that respond to many other relevant biologic stimuli, including temperature, enzymes, and hypoxia.