Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer’s Disease

Scientific report has published a paper on γ-cyclodextrin-enabled crocetin formulation which can deliver crocetin into the brain. [1]

Crocetin (CRT) has shown various neuroprotective effects such as antioxidant activities and the inhibition of amyloid β fibril formation, and thus is a potential therapeutic candidate for Alzheimer’s disease (AD). However, poor water solubility and bioavailability are the major obstacles in formulation development and pharmaceutical applications of CRT. In this study, a novel water-soluble CRT-γ-cyclodextrin inclusion complex suitable for intravenous injection was developed. The inclusion complex was nontoxic to normal neuroblastoma cells (N2a cells and SH-SY5Y cells) and AD model cells (7PA2 cells). Furthermore, it showed stronger ability to downregulate the expression of C-terminus fragments and level of amyloid β in 7PA2 cell line as compared to the CRT free drug. The pharmacokinetics and biodistribution studies showed that CRT-γ-cyclodextrin inclusion complex significantly increased the bioavailability of CRT and facilitated CRT crossing the blood-brain barrier to enter the brain. This data shows a water-soluble γ-cyclodextrin inclusion complex helped to deliver CRT across the blood-brain barrier.

These results provide some meaningful information for pharmaceutical research on CRT for AD therapy, and provide hints for the general development of γ-CD-based drug delivery systems by modifying the chemical structure of γ-CD to deliver other drugs across the BBB with higher efficiency for AD treatment.

Some other references on the cyclodextrins and the BBB are also worth to read [2, 3].

[1] Wong, K.H., Xie, Y., Huang, X. et al. (2020) Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer’s Disease. Sci Rep 10, 3654 . https://doi.org/10.1038/s41598-020-60293-y

[2] Vecsernyés M, Fenyvesi F, Bácskay I, Deli MA, Szente L, Fenyvesi É. (2014) Cyclodextrins, blood-brain barrier, and treatment of neurological diseases. Arch Med Res. 45(8):711-729. doi:10.1016/j.arcmed.2014.11.020

[3 ] Calias P. (2017). 2-Hydroxypropyl-β-cyclodextrins and the Blood-Brain Barrier: Considerations for Niemann-Pick Disease Type C1. Current pharmaceutical design, 23(40), 6231–6238. https://doi.org/10.2174/1381612823666171019164220