Small Molecule Hydrogels\nLoading Small Molecule Drugs\nfrom Chinese Medicine for the Enhanced Treatment of Traumatic Brain\nInjury

Self-assembly of hydrogels for mechanical support and\ndrug delivery\nhas been extensively researched in traumatic brain injury (TBI), where\ntreatment options are limited. The chief challenge is that most self-assembled\nhydrogels rely on high molecular carriers or the incorporation of\nexogenous inactive substances as mediators. It is difficult for these\ndrug delivery systems to achieve clinical translation due to concerns\nregarding biological safety. Here we report a small molecule hydrogel\n(GBR-gel) loading small molecule drugs (glycyrrhizic acid, berberine,\nand rhein) that originated from popular Chinese medicines without\nadditional drug loading or inactive components under physiological\nconditions. In the long run, GBR-gel possesses several advantages,\nincluding ease of preparation, cost-effectiveness, and high biocompatibility.\nAs a proof-of-concept, GBR-gel allows for prompt administration at\nthe site of brain injury to exert potent pharmacodynamic effects.\nFurther single-cell RNA sequencing and experimental validation indicated\nthat GBR-gel can effectively rescue the suppressed glutamatergic synapse\npathway after TBI, thereby attenuating inflammatory responses and\nneural impairments. Our work provides an alternative strategy for\ntimely intervention of TBI.