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Abstract Title:

Delivering Crocetin across the Blood-Brain Barrier by Usingγ-Cyclodextrin to Treat Alzheimer's Disease.

Abstract Source:

Sci Rep. 2020 Feb 27 ;10(1):3654. Epub 2020 Feb 27. PMID: 32107408

Abstract Author(s):

Ka Hong Wong, Yuning Xie, Xiao Huang, Kazunori Kadota, Xin-Sheng Yao, Yang Yu, Xiaoyu Chen, Aiping Lu, Zhijun Yang

Article Affiliation:

Ka Hong Wong

Abstract:

Crocetin (CRT) has shown various neuroprotective effects such as antioxidant activities and the inhibition of amyloidβ 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 ofamyloid β in 7PA2 cell line as compared to the CRT free drug. Both inclusion complex and CRT were able to prevent SH-SY5Y cell death from HO-induced toxicity. 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. This success should fuel further pharmaceutical research on CRT in the treatment for AD, and it should engender research on γ-cyclodextrin with other drugs that have so far not been explored.

Study Type : In Vitro Study

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