Overcoming the Blood-Brain Barrier, Strategies and Advances in Therapeutic Delivery: A Literature Review

Abstract

The treatment options for disorders affecting the central nervous system (CNS) heavily rely on medications to be delivered to the brain, however diverse and effective treatment options are lacking, especially in Alzheimer’s disease (AD) and brain cancers. The passage of drugs into the brain is challenging, due to limited permeability of the blood-brain barrier (BBB). The BBB is a physiological filter for molecules circulating in the bloodstream, playing an essential role in protecting the brain and maintaining its homeostasis. The endothelial cells constituting the microvasculature of the BBB exhibit characteristics such as high levels of tight junctions, adherens junctions and efflux transport proteins, which, together with the lack of capillary fenestrations, impede the ability of drugs to reach CNS targets. Currently available treatments are limited, with invasive neurosurgical interventions and novel non-invasive delivery strategies. Invasive approaches are challenged by significant adverse events and potentially marginal efficacy. Many new methods open prospects for targeted drug deposition in the brain, each with distinct mechanisms of action. These methods comprehend focused ultrasound-mediated disruption of the BBB, innovative physicochemical drug formulations and intranasal pharmacological administrations. The aim of this review is to provide a critical analysis of the current state of drug delivery across the BBB, comparing existing and emerging technologies in the context of neurodegenerative disorders, in particular AD, and brain cancers. A literature search was performed including articles exploring current and evolving methods for drug delivery across the BBB. Considering epidemiological trends highlighting the growing societal burden of neurodegeneration in aging populations and rising incidence of cancers worldwide, it is essential to explore options for effective drug delivery to the brain. The development and optimization of such innovative drug delivery methods holds significant potential for treating neurological disorders: facilitating the use of large molecules, exhibiting more specific cellular targeting but reduced brain permeability, or expediting the formulation of novel molecules bypassing the physiological systems of the BBB. These strategies can improve therapeutic outcomes, reduce side effects, and enhance the quality of life for patients affected with CNS diseases. Continued research is essential to refine and translate these techniques for clinical use.