Recent progress of hydrogel-based strategies for CNS drug delivery.

As a highly specialized biological interface, the blood-brain barrier (BBB) preserves the microenvironment of the central nervous system (CNS) but simultaneously hinders the penetration of many drugs into the brain. It remains a major obstacle in the effective treatment of CNS disorders. To improve drug accumulation in the brain, numerous delivery systems have attracted increasing attention. Among them, hydrogels have emerged as hopeful carriers due to their excellent biocompatibility, suitable hydrophilicity, localized drug delivery, and adjustable physicochemical properties. Recently, researchers have developed lots of hydrogel-based delivery strategies for CNS-targeted therapeutic applications. Current strategies generally fall into two major groups. One strategy involves bypassing the BBB via local direct delivery, and the other is to penetrate the BBB via systemic delivery based on receptor-mediated or adsorption-mediated transport mechanisms, which significantly expanded the therapeutic potential of hydrogels in CNS therapeutics. The present review systematically summarizes current hydrogel-based drug delivery strategies related to the BBB, with particular focus on transport strategies that facilitate drug passage across the BBB.