Development of Polymersomes for Delivery of Therapeutics to the Brain via Intravenous Injection

摘要

Development of an intravenously injectable therapeutic is desirable for treatment of the lysosomal storage disease GM1 gangliosidosis. Current studies in a feline model suggest that treatment of patients may require multiple invasive craniotomies and brain injections, with a further disadvantage of therapeutic gradients radiating from the injection sites. A minimally invasive intravenous injection could allow the therapeutic to be more uniformly distributed via the capillary network in the brain. For this delivery method, polymersomes, therapeuticloaded polymer vesicles, will need to cross the blood-brain barrier (BBB). The BBB is a highly selective, semipermeable membrane, and based on previous in vitro studies, polymersomes will need a diameter of less than 200 nm to transcytose from the blood into the brain [1]. Especially for pharmaceuticals used for rare diseases such as GM1 gangliosidosis, it is important that the formulations are engineered to be stable and have a long shelf life. Thus, therapeutics and carriers need to maintain their properties during processing for long-term storage, which includes cryogenic freezing and lyophilization (freeze-drying).