Novel polyrotaxane for Niemann Pick disease type C treatment

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The team of Gerhard Wenz (Saarland University, Germany) has published a novel polyrotaxane: hydroxypropyl-β-cyclodextrin(HPBCD):poly(decamethylenephosphate) which has several advantages over HPBCD used at present for the treatment of Niemann Pick disease type C (NPC). [1]

This detrimental lysosomal storage disease leads to aberrant accumulation of cholesterol as microcrystalline deposits damaging liver, spleen and brain often causing progressive degeneration of the patient. HPBCD accepted for treatment by both FDA and EMA has poor pharmacokinetic parameters (fast renal clearance) requiring high and frequent doses accompanied by lung- and ototoxicity depending on the route of administration. Several research teams are developing macromolecular carriers for HPBCD to ensure slow release (see: CD-based macromolecular systems in NPC).

The new approach of Wenz’s group is the use of polyalkylene phosphate consisting of decamethylene spacers with high affinity for complexation and biodegradable anionic phosphodiester groups. The degree of polymerization in preparation of the decamethylenephosphate polymeric precursor was determined to be 76, the molecular weight was 35 kDa. HPBCD readily forms complex with this polymer resulting in 18% coverage of HPBCD. For endcapping α-CD was used (3%). The resulting system was taken up by NPC1-deficient cells, and release HPBCD slowly. Cholesterol depleting activity was proved by filipin staining.

This novel polyrotaxane can serve as a long circulating and slow HPBCD-releasing platform.



[1] K. Egele, S. Samaddar, N. Schneider, D. Thompson, G. Wenz: Synthesis of the anionic hydroxypropyl-β-cyclodextrin:poly(decamethylenephosphate) polyrotaxane and evaluation of its cholesterol efflux potential in Niemann–Pick C1 cells.Mater. Chem. B, 2019, 7, 528–537. DOI: 10.1039/c8tb02950d

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