Synthesis of 2-Hydroxypropyl-尾-cyclodextrin/Pluronic-Based Polyrotaxanes via Heterogeneous Reaction as Potential Niemann-Pick Type C Therapeutics

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• 作者：Yawo A. Mondjinou ; Leslie A. McCauliff ; Aditya Kulkarni ; Lake Paul ; Seok-Hee Hyun ; Zhaorui Zhang ; Zhen Wu ; Mary Wirth ; Judith Storch ; David H. Thompson
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：December 9, 2013
• 年：2013
• 卷：14
• 期：12
• 页码：4189-4197
• 全文大小：469K
• 年卷期：v.14,no.12(December 9, 2013)
• ISSN：1526-4602

文摘

Five polyrotaxanes were synthesized by threading 2-hydroxypropyl-尾-cyclodextrin (HP-尾-CD) onto a variety of 伪,蠅-ditriethylenediamino-N-carbamoyl-poly-(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (Pluronic) triblock copolymers using a two-pot strategy under heterogeneous, nonaqueous conditions. The threaded HP-尾-CD units were retained on the pseudopolyrotaxane precursors by end-capping the branched diamine termini with sodium 2,4,6-trinitrobenzene sulfonate. Inclusion of the Pluronic copolymers within the HP-尾-CD cavities was more favorable in nonpolar solvents, such as diethyl ether and n-hexane, both of which gave better coverage ratios than polar solvents. ¹H NMR and MALDI-TOF were used to estimate the average molecular weights of the purified polyrotaxane products. A globular morphology of aggregated polyrotaxanes was observed by tapping-mode AFM imaging of dried samples. Treatment of Niemann-Pick C (NPC) type 2-deficient fibroblasts with the polyrotaxane derivatives produced substantial reductions in sterol accumulation, as seen by diminished filipin staining in these cells, suggesting that Pluronic-based polyrotaxanes may be promising vehicles for delivery of HP-尾-CD to cells with abnormal cholesterol accumulation.