The study investigates the use of convection-enhanced delivery to improve the distribution of large and small molecules in the brain. The researchers used 111In-labeled transferrin (111In-Tf) and [14C]sucrose as model compounds to demonstrate that maintaining a pressure gradient during interstitial infusion can generate bulk flow through the brain interstitium, enhancing the distribution of these molecules over centimeter distances. The volume of distribution (Vd) containing at least 1% concentration of the infused solution increased linearly with the infusion volume for both 111In-Tf and [14C]sucrose. After 24 hours, the distribution of 111In-Tf was more homogeneous and had penetrated into gray matter. This method, by supplementing simple diffusion, can achieve drug concentrations orders of magnitude greater than systemic levels, providing a promising approach to enhance drug delivery to the brain and potentially treat neurological disorders.The study investigates the use of convection-enhanced delivery to improve the distribution of large and small molecules in the brain. The researchers used 111In-labeled transferrin (111In-Tf) and [14C]sucrose as model compounds to demonstrate that maintaining a pressure gradient during interstitial infusion can generate bulk flow through the brain interstitium, enhancing the distribution of these molecules over centimeter distances. The volume of distribution (Vd) containing at least 1% concentration of the infused solution increased linearly with the infusion volume for both 111In-Tf and [14C]sucrose. After 24 hours, the distribution of 111In-Tf was more homogeneous and had penetrated into gray matter. This method, by supplementing simple diffusion, can achieve drug concentrations orders of magnitude greater than systemic levels, providing a promising approach to enhance drug delivery to the brain and potentially treat neurological disorders.