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<p>Curcumin shows promise in treating neurodegenerative diseases due to its anti – inflammatory and neuroprotective effects. However, its clinical use is limited by poor bioavailability and restricted blood brain barrier (BBB) penetration. Intranasal delivery offers a non – invasive route that bypasses the BBB and first – pass metabolism, enabling direct brain targeting. This study employed cow milk derived exosome as nanocarrier to deliver curcumin to the brain via intranasal route. A combination of low speed centrifugation process and size exclusion chromatography method was used to preserve the structure of exosome. The Optimized Cow milk-derived curcumin-loaded exosome formulation (CUR@EXO) formulation was prepared and it was further characterized, In vitro drug release study, safety profile in nasal and brain tissue, brain biodistribution and stability of the CUR@EXO were determined. Results demonstrated the successful isolation of cow milk exosomes with an obtained size of 116.7&#xa0;nm with Polydispersity Index 0.092. Transmission electron microscopy and Scanning electron microscopy images shows spherical exosomes with double-layer membrane. In-vitro drug release study of the exosome reveals the sustained release manner and fickian diffusion mechanism of CUR@EXO in artificial cerebrospinal fluid medium. Brain toxicity and Ex-vivo nasal toxicity study ensure the safety of CUR@EXO in nasal and brain tissue. The In-vivo study depicted the concentration of curcumin released from CUR@EXO into brain after intranasal administration, and the stability study indicated that the formulation is most stable at -80℃ and − 20℃. From the results, it can be concluded that exosome is a potential nanocarrier that exhibits efficient intranasal delivery to the brain.</p> Graphical Abstract <p></p>

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Development of Nose-to-Brain Targeted Cow Milk-Derived Exosomes for Enhanced Delivery of Curcumin to the Brain

  • 期刊论文

  • 发表日期：

    2026年3月3日

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  • Himakshi Baruah,
  • Anupam Sarma,
  • Mridusmita Das,
  • Hrishikesh Sarma,
  • Debojeet Basak,
  • Bhrigu Kumar Das

摘要

Curcumin shows promise in treating neurodegenerative diseases due to its anti – inflammatory and neuroprotective effects. However, its clinical use is limited by poor bioavailability and restricted blood brain barrier (BBB) penetration. Intranasal delivery offers a non – invasive route that bypasses the BBB and first – pass metabolism, enabling direct brain targeting. This study employed cow milk derived exosome as nanocarrier to deliver curcumin to the brain via intranasal route. A combination of low speed centrifugation process and size exclusion chromatography method was used to preserve the structure of exosome. The Optimized Cow milk-derived curcumin-loaded exosome formulation (CUR@EXO) formulation was prepared and it was further characterized, In vitro drug release study, safety profile in nasal and brain tissue, brain biodistribution and stability of the CUR@EXO were determined. Results demonstrated the successful isolation of cow milk exosomes with an obtained size of 116.7 nm with Polydispersity Index 0.092. Transmission electron microscopy and Scanning electron microscopy images shows spherical exosomes with double-layer membrane. In-vitro drug release study of the exosome reveals the sustained release manner and fickian diffusion mechanism of CUR@EXO in artificial cerebrospinal fluid medium. Brain toxicity and Ex-vivo nasal toxicity study ensure the safety of CUR@EXO in nasal and brain tissue. The In-vivo study depicted the concentration of curcumin released from CUR@EXO into brain after intranasal administration, and the stability study indicated that the formulation is most stable at -80℃ and − 20℃. From the results, it can be concluded that exosome is a potential nanocarrier that exhibits efficient intranasal delivery to the brain.

Graphical Abstract