Delivery of a peptide-drug conjugate targeting the blood brain barrier improved the efficacy of paclitaxel against glioma

The challenge of effectively delivering therapeutic agents to the brain has created an entire field of active research devoted to overcoming the blood brain barrier (BBB) and efficiently delivering drugs to the brain. Angiopep-2 can trigger transcytosis and traverse the BBB by recognizing low-density lipoprotein related protein-1 (LRP-1) expressed on the brain capillary endothelial cells. Here, we designed a novel strategy for the delivery of drugs to the brain. The novel drug delivery system was a combination of a receptor-targeting ligand, such as low-density lipoprotein related protein 1, and a cell-penetrating peptide (CPP). It was hypothesized that this conjugate will enhance the delivery of associated therapeutic cargo across the BBB and increase the permeability of a solid tumor. Our findings indicate that the combination of these two agents in a delivery vehicle significantly improved translocation of small molecules (paclitaxel) into the brain compared to the vehicle treatment, which contained only receptor-targeting ligand. The application of this strategy could potentially expand the horizons for the treatment of central nervous system disorders.