Nanoparticles modified with glucose analogs to enhance the permeability of the blood–brain barrier and their accumulation in the epileptic brain†

Abstract

Drug delivery for epilepsy treatment faces enormous challenges, where the sole focus on enhancing the ability of drugs to penetrate the blood–brain barrier (BBB) through ligand modification is insufficient because of the absence of seizure-specific drug accumulation. In this study, an amphipathic drug carrier with a glucose transporter (GLUT)-targeting capability was synthesised by conjugating 2-deoxy-2-amino-D-glucose (2-DG) to the model carrier DSPE-PEG_2k. A 2-DG-modified nano drug delivery system (NDDS) possessing robust stability and favourable biocompatibility was then fabricated using the nanoprecipitation method. The results showed that the 2-DG-modified NDDS exhibited enhanced cellular uptake by brain capillary endothelial cells and neuronal cells. Most importantly, the 2-DG-modified NDDS exhibited enhanced BBB penetration and brain accumulation, especially in the epileptic brain, thus achieving seizure-based on-demand drug delivery. Our study provides a simple and smart strategy for the delivery of anti-seizure medicines.