Hydrogen bond-enhanced nanogel delivery system for potential intranasal therapy of Parkinson's disease

• The hydrogen bond-enhanced nanogel system can be used as a sustained-release carrier for non-invasive drug administration. • Nanogel systems utilize the hydrogen bonding sites of active small molecules to improve their stability and loading rate in drug carriers without chemical modification. • Glycyrrhizic acid is involved in the construction of the nanogel system and is also a potential drug for PD treatment. Parkinson's disease (PD) is a severe neurodegenerative disease with a high incidence in the elderly and is mainly treated by drugs. The blood–brain barrier (BBB) limits the entry of oral neuroactive drugs to the brain, reducing drug concentration and affecting the treatment of PD. Nanotechnology-based drug delivery systems, especially thermosensitive systems, allow drug access to the brain via the nose-brain pathway, which is not limited by the presence of BBB. These delivery systems demonstrate outstanding performance in enhancing brain accumulation of active drugs, improving the loading capacity and stability. In this study, a nano-hydrogel delivery system composed of hydrogen bond-enhanced nanogel and thermosensitive gel is prepared for the effective delivery of albiflorin to treat PD. Importantly, the glycyrrhizic acid acts as a hydrogen bond crosslinker and adjunctive drug to prevent the premature release of albiflorin and achieve synergistic therapeutic performance. Compared to free drugs, the nano-hydrogel delivery system provides superior efficacy due to the enhanced stability. Moreover, this nano-hydrogel delivery system exhibits a selective brain distribution and accumulation and good antioxidant and anti-inflammation effects. This work demonstrates that this intranasal nanogel may function as a promising drug delivery system in treating PD.