To investigate the use of perillaldehyde (PAE) for treating plateau insomnia and to develop a stable intranasal PAE nanomicelles in situ gel (PAE/NMs-INSG).

A mouse model of plateau insomnia was established in this study. Sleep latency/duration and brain melatonin/gamma-aminobutyric acid levels were also assessed. PAE/NMs were prepared via thin-film hydration and optimized using the Box–Behnken design. An in situ gel was formulated using poloxamer 407 and chitosan. The gel properties (pH, viscosity, and rheology), in vitro release, and stability were characterized.

PAE alleviated symptoms of plateau insomnia. The optimized PAE/NMs had a size of 92.40 nm, polydispersity index of 0.246, encapsulation efficiency of 79.50%, and drug loading of 10.60%. The final PAE/NMs-INSG (18% P407, 0.25% chitosan) was spherical, with a suitable pH (5.4) and viscosity (5.024 Pa s), and exhibited viscoelastic behavior. PAE/NMs-INSG showed sustained release and improved the stability of PAE.

PAE, administered intranasally, effectively alleviates plateau insomnia. The developed PAE/NMs-INSG enhances PAE stability and exhibits sustained release, thereby offering a promising strategy.