Jump to main content
Jump to site search


Synthesis of the Anionic Hydroxypropyl-β-cyclodextrin:Poly(decamethylenephosphate) Polyrotaxane and Evaluation of its Cholesterol Efflux Potential in Niemann-Pick C1 Cells

Abstract

Niemann–Pick type C disease (NPC) is a lysosomal storage disease that is characterized by a progressive accumulation of unesterified cholesterol in the lysosomes leading to organ damage from cell dysfunction. Hydroxypropyl-β-cyclodextrin (HP-β-CD) is an attractive drug candidate for treating NPC, as it diminishes cholesterol accumulation in NPC cells. Systemic HP-β-CD treatment, however, is limited by rapid renal clearance. We designed a new anionic HP-β-CD polyrotaxane to act as a slow release formulation based on a polyalkylene phosphate core to improve the pharmacokinetics. The polyalkylene phosphate comprises hydrophobic decamethylene spacers linked by biodegradable anionic phosphodiester bonds. HP-β-CD was threaded onto this polymer first and α-CD afterwards to prevent burst release of the threaded HP-β-CD. Our findings show that HP-β-CD was slowly released from the watersoluble polyrotaxane over a 30 days period. The polyrotaxane provided persistently diminished cholesterol levels in NPC1 cells by 20% relative to untreated cells. These results demonstrate the therapeutic potential of this novel HP-β-CD polyrotaxane for the mobilization of aberrantly stored cholesterol in NPC1 cells

Back to tab navigation

Supplementary files

Publication details

The article was received on 08 Nov 2018, accepted on 06 Dec 2018 and first published on 07 Dec 2018


Article type: Paper
DOI: 10.1039/C8TB02950D
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
  •   Request permissions

    Synthesis of the Anionic Hydroxypropyl-β-cyclodextrin:Poly(decamethylenephosphate) Polyrotaxane and Evaluation of its Cholesterol Efflux Potential in Niemann-Pick C1 Cells

    K. Egele, S. Samaddar, N. Schneider, D. H. Thompson and G. Wenz, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB02950D

Search articles by author

Spotlight

Advertisements