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

Ka Hong Wong, Yuning Xie, Xiao Huang, Kazunori Kadota, Xin Sheng Yao, Yang Yu, Xiaoyu Chen, Aiping LYU, Zhijun YANG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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. Both inclusion complex and CRT were able to prevent SH-SY5Y cell death from H2O2-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.

Original languageEnglish
Article number3654
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

Scopus Subject Areas

  • General

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