Impact of Mixed β-Cyclodextrin Ratios on Pluronic Rotaxanation Efficiency and Product Solubility

Water-soluble polyrotaxanes have been prepared under heterogeneous conditions from mixtures of beta-cydodextrin (beta-CD), 2-hydroxypropyl-beta-cydodextrin (HP-beta-CD), methyl-beta-cyclodextrin, or 6-monoazido-beta-cydodextrin with 4-sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) and Pluronic L81 copolymer modified with cholesterol end caps. Threading reactions gave polyrotaxane products in modest chemical yield that were reflective of the beta-CD feed ratios in the reaction. Polyrotaxanes containing mixtures of HP-beta-CD and SBE-beta-CD were screened and found to be biologically active in an in vitro model of Niemann-Pick Type C disease where they mobilize aberrantly stored cholesterol similarly to monomeric cyclodextrin controls.