Compositions containing inclusion complexes
View Patent ↗The invention provides a composition containing particulate composite of a polymer and a therapeutic agent. The composition also contains a complexing agent. The polymer interacts with the complexing agent in a host-guest or a guest-host interaction to form an inclusion complex. A therapeutic composition of the invention may be used to deliver the therapeutic agent and to treat various disorders. Both the polymer of the particulate composite and the complexing agent may be used to introduce functionality into the therapeutic composition. The invention also relates to a method of preparing a composition. The method combines a therapeutic agent, a polymer having host or guest functionality, and a complexing agent having guest or host functionality to form the therapeutic composition. The complexing agent forms an inclusion complex with the polymer. The invention also relates to a method of delivering a therapeutic agent. According to the method, a therapeutically effective amount of a therapeutic composition of the invention is administered to a mammal (e.g. person or animal) in recognized need of the therapeutic. Also disclosed are compounds having the formula:
1. A composition comprising:
a linear cyclodextrin-containing polymer,
a therapeutic agent, and
an inclusion complex of said polymer and a complexing agent,
wherein
the complexing agent comprises a ligand for cell targeting, and
the polymer has host functionality, and
wherein said complexing agent is a compound of the formula:
wherein J is —NH—, —C(═O)NH—(CH 2 ) d —, —NH—C(═O)—(CH 2 ) d —, —CH 2 SS—, —C(═O)O—(CH 2 ) e —O—P(═O)(O—(CH 2 ) e -Ad)O—,
—NH(C═O)—CH(R 1 )—NH—(C═O)—CH(R 1 )—NH—;
Ad is adamantyl;
R 1 is —(CH 2 ) a —CO 2 H, an ester or salt thereof; or —(CH 2 ) a —CONH 2 ;
PEG is —O(CH 2 CH 2 O) z —, where z varies from 2 to 500;
L is H, —NH 2 , —NH—(C═O)—(CH 2 ) e —(C═O)—CH 2 , —S(═O) 2 —HC═CH 2 —, —SS—, —C(═O)O— or a carbohydrate residue;
Functional Group comprises a ligand for cell targeting;
a is 0 or 1;
b is 0 or 1;
d ranges from 0 to 6;
e ranges from 1 to 6;
n ranges from 0 to 6;
y is 1; and
x is 1.
2. A composition of claim 1 , wherein said complexing agent has guest functionality.
3. A composition of claim 1 , wherein said complexing agent has host functionality.
4. A composition of claim 1 , wherein said polymer has host and guest functionality and comprising a mixture of complexing agents having guest and host functionality.
5. A composition of claim 1 , wherein said host functionality is selected from cyclodextrin, a carcerand, a cavitand, a crown ether, a cryptand, a cucurbituril, a calixarene, a spherand or a mixture thereof.
6. A composition of claim 1 , wherein said complexing agent further comprises a spacer group.
7. A composition of claim 2 , wherein said guest functionality is adamantane.
8. A composition of claim 2 , 3 , 4 , or 7 , wherein said host functionality is a cyclodextrin.
9. A composition of claim 1 or 2 , wherein the ligand is transferrin.
10. A composition of claim 1 or 2 , wherein said therapeutic agent is selected from an antibiotic, a steroid, a polynucleotide, small molecule pharmaceutical, a virus, a plasmid, a peptide, a peptide fragment, a chelating agent, a biologically active macromolecule, and any combination of these.
11. A composition of claim 10 , wherein said therapeutic agent is a polynucleotide.
12. A method of delivering a therapeutic comprising the step of administering to a person in recognized need of the therapeutic agent a therapeutically effective amount of a composition of claim 1 , 2 , or 4 .
13. The composition of claim 1 , wherein the complexing agent further comprises a moiety that stabilizes the composition under biological conditions relative to a composition of the polymer and therapeutic agent alone.
14. The composition of claim 1 , wherein the complexing agent further comprises a therapeutic agent that is reversibly bound to the complexing agent.
15. The composition of claim 1 , wherein the polymer comprises at least one host moiety that forms an inclusion complex with at least one guest moiety of the complexing agent.
16. The composition of claim 1 , wherein the polymer comprises at least one guest moiety that forms an inclusion complex with at least one host moiety of the complexing agent.
17. The composition of claim 1 , wherein the linear cyclodextrin-containing polymer comprises cyclodextrin moieties in the backbone of the polymer.
18. The composition of claim 1 , wherein the linear cyclodextrin-containing polymer contains at least one cyclodextrin moiety in a pendant chain of the linear cyclodextrin-containing polymer.
19. The composition of claim 1 , wherein the complexing agent comprises at least one polymer portion.
20. The composition of claim 19 , wherein at least one polymer portion of the complexing agent comprises PEG or derivatives thereof
21. The composition of claim 1 , wherein the complexing agent comprises at least one polymer portion.
22. The composition of claim 6 , wherein the spacer group comprises at least one polymer portion.
23. A composition of claim 1 , wherein the polymer, therapeutic agent, and the complexing agent are separate molecules.
24. The composition of claim 1 , wherein the therapeutic agent is an anti-cancer agent.