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

Authors :
Judith Storch
David H. Thompson
Leslie A. McCauliff
Aditya Kulkarni
Seok-Hee Hyun
Mary J. Wirth
Zhen Wu
Zhaorui Zhang
Lake N. Paul
Yawo A. Mondjinou
Source :
Biomacromolecules. 14:4189-4197
Publication Year :
2013
Publisher :
American Chemical Society (ACS), 2013.

Abstract

Five polyrotaxanes were synthesized by threading 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) onto a variety of α,ω-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-β-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-β-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. (1)H 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-β-CD to cells with abnormal cholesterol accumulation.

Details

ISSN :
15264602 and 15257797
Volume :
14
Database :
OpenAIRE
Journal :
Biomacromolecules
Accession number :
edsair.doi.dedup.....63652aa9b2c9a66b1734c535877bf335