Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain

The unique anatomical and physiological features of the blood-brain barrier (BBB), while essential for maintenance of normal brain health, present significant challenges in development of effective therapies for neurological disorders from a drug delivery perspective. This is particularly the case for biotherapeutics such as monoclonal antibodies, which have a restricted brain distribution following systemic administration. While the BBB is often presumed to be leaky in tumors within the brain, it is important to recognize that the degree of compromise is highly variable with certain regions such as micro-tumors and infiltrative margins of larger tumors having a functional and intact BBB. Given this, limited delivery of therapeutic agents across the BBB poses a critical challenge that needs to be overcome to improve treatment outcomes in patients diagnosed with tumors in the brain. Here, we review various considerations relevant to distribution of biologics to tumors in the brain, both primary brain tumors and secondary metastases to the brain. We discuss the various strategies being explored to enhance the delivery of biotherapeutics across the BBB and outline the associated limitations. We also highlight the cross-talk between the drug delivery strategies for neurological disorders and neuro-oncology indications as an important area of research that should be encouraged.