Therapeutic and imaging compositions and uses thereof
Various embodiments of the present invention are directed to polyrotaxanes comprising a poloxamer core and at least one cyclodextrin and methods for treating Niemann-Pick type C (NPC) and imaging (e.g., MRI) using the polyrotaxanes various embodiments of the present invention.
1. A polyrotaxane comprising the general formula:
or a salt thereof,
wherein:
n is an integer from 1 to 30;
C and C′ are the same or different and represent endcapping groups of the formula:
wherein:
L 1 is a (C 1 -C 6 )hydrocarbylene group,
G 1 and G 2 , together, form a radical having the formula:
wherein each L 2 is independently a bond or acyl; each G 3 is a substituted or unsubstituted (C 6 -C 50 )hydrocarbyl group, interrupted by 0 to 5 groups chosen from —O—, —NH—, and —S—; and
each s is independently an integer from 1 to 5; and
t is an integer from 2 to 5:
B is a poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEG-PPG-PEG) triblock copolymer; and
A is a beta cyclodextrin;
wherein G 3 is not a substituted or unsubstituted (C 6 -C 12 )aryl group.
2. The polyrotaxane of claim 1 , wherein G 3 is a substituted or unsubstituted —O—(C 6 -C 50 )alkyl group.
3. The polyrotaxane of claim 1 , wherein G 3 is a cholesteryl group.
4. The polyrotaxane of claim 1 , wherein n is an integer from 5 to 15.
5. The polyrotaxane of claim 1 , wherein n is an integer from 3 to 11.
6. A pharmaceutical composition comprising the polyrotaxane of claim 1 and a pharmaceutically acceptable carrier.
7. The polyrotaxane of claim 1 , wherein the poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEG-PPG-PEG) triblock copolymer has the formula:
wherein each R 5 is methyl; d is an integer from about 100 to about 800; and q is an integer from about 100 to about 800.
8. The polyrotaxane of claim 7 , wherein d+q is from about 100 to about 800.