Polyrotaxanes bearing mixed cyclodextrin species and uses thereof

1. A polyrotaxane having the general formula:

or salts thereof,

wherein:

each m, m′, n and n is, independently, an integer from 0 to 30, with the proviso that m+m′+n+n′ is from about 4 to about 30;

C and C′ are the same or different and represent end capping groups of the formula:

wherein each L 2 is independently a bond or (C 1 -C 6 )acyl; each G 3 is a steroid group; and each s is independently an integer from 1 to 6;

B represents:

to which the endcapping groups are covalently attached to B via a (C 1 -C 6 )hydrocarbylene group;

wherein R 5 is methyl; d is an integer from about 1 to about 800; and q is an integer from about 6 to about 800; and

A and A′ each independently represent the macrocyclic host molecule of the general formula (I):

wherein:

A and A′ can be the same or different;

x is an integer from 0 to 8; Z is O or NH;

each R 1 and R 2 is, independently, hydrogen or a substituted or unsubstituted (C 1 -C 6 )hydrocarbyl group.

2. The polyrotaxane of claim 1 , wherein C and C′ are the same or different and represent end capping groups of the formula:

wherein each L 2 is independently a (C 1 -C 6 )acyl.

3. The polyrotaxane of claim 1 , wherein R 1 is a substituted (C 1 -C 6 )hydrocarbyl group.

4. The polyrotaxane of claim 1 , wherein m+m′+n+n′ is from about 5 to about 20.

5. The polyrotaxane of claim 1 , wherein A is hydroxypropyl-β-cyclodextrin (HPβCD).

6. The polyrotaxane of claim 1 , wherein A′ is 4-sulfobutylether-β-cyclodextrin (SBEβCD).

7. The polyrotaxane of claim 1 , wherein A is hydroxypropyl-β-cyclodextrin and m+n is from about 2 to about 10; and A′ is 4-sulfobutylether-β-cyclodextrin and m′+n′ is from about 2 to about 10.

8. The polyrotaxane of claim 1 , wherein the polyrotaxane is HPβCD/SBEβCD-F127 (wherein d=200 and q=65); HPβCD/SBEβCD-F68 (wherein d=151 and q=29); HPβCD/SBEβCD-L35 (wherein d=22 and q=16); HPβCD/SBEβCD-L64 (wherein d=26 and q=30); or HPβCD/SBEβCD-L81 (wherein d=6.25 and q=43), wherein:

the polyrotaxane has a weight average molecular weight of about 20,000 g/mol to about 50,000 g/mol as determined by GPC analysis;

HPβCD is a macrocyclic host of the formula (I) wherein each R′ is H, and Z is O; and

the groups C and C′ of the formula:

wherein each s is 2; each L 2 is C(O); and the steroid group is a cholesteryl group that is covalently attached to the group B of the formula:

via a C(O) group.

9. The polyrotaxane of claim 8 , wherein the polyrotaxne comprises from about 1 to about 10 HPβCD molecules and from about 1 to about 10 SBEβCD.

10. A pharmaceutical composition comprising the polyrotaxane of claim 1 and a pharmaceutically acceptable carrier.

11. A method for treating Niemann-Pick type C (NPC) comprising administering a therapeutically effective amount of a polyrotaxane as in claim 1 to a subject in need thereof.

12. The polyrotaxane of claim 1 , wherein the steroid group is a cholesteryl group.