Beyond the Walls of Troy: A Scoping Review on Pharmacological Strategies to Enhance Drug Delivery Across the Blood-Brain Barrier and Blood-Tumor Barrier.

The blood-brain barrier (BBB) is a highly selective interface between the bloodstream and the brain that prevents systemically administered therapeutics from effectively reaching tumor cells. As tumors progress, this barrier undergoes structural and functional alterations, giving rise to the blood-tumor barrier (BTB)-a pathologically modified structure that, despite increased permeability, often exhibits heterogeneous and clinically insufficient drug transport. Although a new generation of therapies is promising, their therapeutic potential cannot be realized unless the challenges posed by these barriers are effectively addressed. Various pharmacological strategies were explored to enhance brain tumor drug delivery. These include receptor-mediated disruption, inhibition of efflux transporters, and the engineering of delivery platforms that leverage endogenous transport pathways-such as carrier-mediated, adsorptive-mediated, and receptor-mediated mechanisms-as well as cell-mediated drug delivery. This review synthesizes (1) the BBB and BTB's structural characteristics; (2) the influence of the tumor microenvironment (TME) on drug delivery; (3) pharmacological strategies to enhance drug accumulation within brain tumors; (4) the integration of pharmacological methods with neurosurgical techniques to enhance drug delivery. As efforts to improve drug delivery across the BBB and BTB accelerate, this review aims to map the current landscape of pharmacological approaches for enhancing drug penetration into brain tumors.