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<p>Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is the leading clinical cause of dementia. Magnolol has promising therapeutic potential for AD. However, its poor aqueous solubility and the challenge of achieving brain-targeted delivery have severely hindered its clinical usage. This study designed a thermosensitive in situ hydrogel nasal spray for co-delivery of magnolol nanosuspensions and berberine, targeting AD treatment via nose-to-brain delivery. The magnolol nanosuspensions were prepared via a wet-milling approach to improve the drug’s solubility. A thermosensitive hydrogel based on poly(N-isopropylacrylamide) (PNIPAM) was synthesized and formulated as an in situ nasal spray to enable brain-targeted co-delivery of the two drugs. In vitro PC12 cells AD models and in vivo mice was used to evaluation the thermosensitive multifunctional in-situ hybrid gel effectiveness and distribution. Morphological characterization confirmed successful preparation of magnolol nanosuspensions with a mean particle size of 220 ± 10&#xa0;nm, which exhibited a high dissolution rate of 82.36 ± 1.62% within 300&#xa0;min. The nanosuspensions were embedded in the hydrogel, which has a lower critical solution temperature (LCST) of approximately 32&#xa0;°C - allowing rapid phase transition in the nasal cavity (local temperature ~ 35&#xa0;°C). On PC12 cells and mice AD models, the thermosensitive hydrogel co-delivery system increased cell survival by 27.13% and significantly enhanced drug accumulation in the brain. This multifunctional drug delivery system provides an efficient strategy for the brain-targeted delivery of magnolol nanosuspensions and berberine, offering a promising approach for AD treatment.</p>

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Thermosensitive In Situ Hydrogel-Mediated Nose-to-Brain Co-Delivery of Magnolol Nanosuspensions and Berberine for Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2026年4月27日

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  • Yingying Ma,
  • Linying Xue,
  • Yancai Wang

摘要

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is the leading clinical cause of dementia. Magnolol has promising therapeutic potential for AD. However, its poor aqueous solubility and the challenge of achieving brain-targeted delivery have severely hindered its clinical usage. This study designed a thermosensitive in situ hydrogel nasal spray for co-delivery of magnolol nanosuspensions and berberine, targeting AD treatment via nose-to-brain delivery. The magnolol nanosuspensions were prepared via a wet-milling approach to improve the drug’s solubility. A thermosensitive hydrogel based on poly(N-isopropylacrylamide) (PNIPAM) was synthesized and formulated as an in situ nasal spray to enable brain-targeted co-delivery of the two drugs. In vitro PC12 cells AD models and in vivo mice was used to evaluation the thermosensitive multifunctional in-situ hybrid gel effectiveness and distribution. Morphological characterization confirmed successful preparation of magnolol nanosuspensions with a mean particle size of 220 ± 10 nm, which exhibited a high dissolution rate of 82.36 ± 1.62% within 300 min. The nanosuspensions were embedded in the hydrogel, which has a lower critical solution temperature (LCST) of approximately 32 °C - allowing rapid phase transition in the nasal cavity (local temperature ~ 35 °C). On PC12 cells and mice AD models, the thermosensitive hydrogel co-delivery system increased cell survival by 27.13% and significantly enhanced drug accumulation in the brain. This multifunctional drug delivery system provides an efficient strategy for the brain-targeted delivery of magnolol nanosuspensions and berberine, offering a promising approach for AD treatment.