Endogenous Polysialic Acid Based Micelles for Calmodulin Antagonist Delivery against Vascular Dementia

Xiao Juan Wang, Yin Ping Gao, Nan Nan Lu, Wei Shuo Li, Ji Fang Xu, Xiao Ying Ying, Gang Wu, Mei Hua Liao, Chao Tan, Ling Xiao Shao, Ying Mei Lu, Chen Zhang, Kohji Fukunaga, Feng Han, Yong Zhong Du

研究成果: Article査読

16 被引用数 (Scopus)

抄録

Clinical treatment for vascular dementia still remains a challenge mainly due to the blood-brain barrier (BBB). Here, a micelle based on polysialic acid (PSA), which is a hydrophilic and endogenous carbohydrate polymer, was designed to deliver calmodulin antagonist for therapy of vascular dementia. PSA was first chemically conjugated with octadecylamine (ODA), and the obtained PSA-ODA copolymer could self-assemble into micelle in aqueous solution with a 120.0 μg/mL critical micelle concentration. The calmodulin antagonist loaded PSA-ODA micelle, featuring sustained drug release behavior over a period of 72 h with a 3.6% (w/w) drug content and a 107.0 ± 4.0 nm size was then fabricated. The PSA-ODA micelle could cross the BBB mainly via active endocytosis by brain endothelial cells followed by transcytosis. In a water maze test for spatial learning, calmodulin antagonist loaded PSA-ODA micelle significantly reduced the escape latencies of right unilateral common carotid arteries occlusion (rUCCAO) mice with dosage significantly reduced versus free drug. The decrease of hippocampal phospho-CaMKII (Thr286/287) and phospho-synapsin I (Ser603) was partially restored in rUCCAO mice following calmodulin antagonist loaded PSA-ODA micelle treatment. Consistent with the restored CaMKII phosphorylation, the elevation of BrdU/NeuN double-positive cells in the same context was also observed. Overall, the PSA-ODA micelle developed from the endogenous material might promote the development of therapeutic approaches for improving the efficacy of brain-targeted drug delivery and have great potential for vascular dementia treatment.

本文言語English
ページ(範囲)35045-35058
ページ数14
ジャーナルACS Applied Materials and Interfaces
8
51
DOI
出版ステータスPublished - 2016 12 28

ASJC Scopus subject areas

  • 材料科学(全般)

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