Preparation and evaluation of a nasal nanogel formulation of perillaldehyde for treating plateau insomnia

Abstract

Objective: 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).

Methods: 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. Anin situ gel was formulated using poloxamer 407 and chitosan. The gel properties (pH, viscosity, and rheology), in vitro release, and stability were characterized.

Results: 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.

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

Keywords

Perillaldehyde / Plateau insomnia / Nanomicelles / Nasal gel / Quality assessment

Funding

This work was supported by the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202207), the Chinese Medicine Preparation Technology and Equipment Innovation Team of the Jiangxi University of Chinese Medicine (CXTD22006), and the Jiangxi University of Chinese Medicine 2025 Annual University-Level Graduate Student Innovation Special Fund Project (XJ-S202542). Open Fund Project of the Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine (201802).

CRediT authorship contribution statement

Qian Li: Investigation, software, formal analysis, visualization, and writing – original draft. Jiaqiao Li: Data curation, formal analysis, validation, visualization, and writing – original draft. Pengyi Hu: Conceptualization and writing – review & editing. Pengfei Yue: Methodology, software, and writing –review & editing. Hongxia Zhu: Methodology, software, and writing –review & editing. Qunlin Zhang: Methodology, software, and writing –review & editing. Qin Zheng: Conceptualization, funding acquisition, supervision, and writing – review & editing.

Declaration of competing interest

The authors declare that there are no conflicts of interest.

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