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 o

SUBMITTER: Egele K 

PROVIDER: S-EPMC6675466 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature