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 compound of the formula:
wherein PEG is polyethylene glycol.
2. The compound of claim 1 , wherein said PEG has a molecular weight between about 500 and about 10,000 Daltons.
3. The compound of claim 1 , wherein said PEG has a molecular weight of about 10,000 Daltons.
4. The compound of claim 1 , wherein said PEG has a molecular weight of about 5,000 Daltons.
5. The compound of claim 1 , further comprising a functional group linked to said PEG.
6. The compound of claim 5 , wherein said functional group is selected from a ligand, nuclear localization signal, endosomal release peptide, endosomal release polymer, a therapeutic agent, a stabilizing polymer/hydrophilic polymer for stabilization, a spacer group, and any combination of these.
7. The compound of claim 6 , wherein said spacer group is selected from a direct bond, a phosphate group, polyethylene glycol, and a short anionic peptide sequence.
8. The compound of claim 6 , wherein said ligand is transferrin.
9. A composition comprising:
a) a cyclodextrin-containing polymer;
b) a therapeutic agent; and
c) said compound of claim 1 .
10. The composition of claim 9 , wherein said cyclodextrin-containing polymer comprises a β-cyclodextrin.
11. The composition of claim 9 , 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, or any combination of these.
12. The composition of claim 11 , wherein said therapeutic agent is a polynucleotide.
13. The composition of claim 9 , wherein said composition has a zeta potential that is lower than +5 mV.
14. The composition of claim 13 , wherein said zeta potential zero or negative.
15. The composition of claim 14 , wherein said zeta potential is negative.
16. A method of delivering a therapeutic agent comprising administering to a person in recognized need of the therapeutic agent a therapeutically effective amount of a composition of claim 9 .
17. A method of preparing said compound of claim 1 comprising:
a) reacting H-Glu(Bn)-OH with Z-Glu(Bn)-OSu, to generate Z-Glu(Bn)-Glu(Bn)-OH, wherein (Bn) represents a benzyl group;
b) reacting Z-Glu(Bn)-Glu(Bn)-OH with 1-adamantanemethylamine to generate:
c) hydrogenating (II) to generate:
d) reacting (III) with an mPEG-derivative to generate said compound of claim 1 .
18. The method of claim 17 , wherein said PEG has a molecular weight of between about 500 and about 10,000 Daltons.
19. The method of claim 17 , wherein said PEG has a molecular weight of about 10,000 Daltons.
20. The method of claim 17 , wherein said PEG has a molecular weight of about 5,000 Daltons.
21. The method of claim 17 , further comprising linking a functional group to said PEG.
22. The method of claim 21 , wherein said functional group is selected from a ligand, nuclear localization signal, endosomal release peptide, endosomal release polymer, a therapeutic agent, a stabilizing polymer/hydrophilic polymer for stabilization, a spacer group, and any combination of these.
23. The method of claim 22 , wherein said spacer group is selected from a direct bond, a phosphate group, polyethylene glycol, and a short anionic peptide sequence.
24. The method of claim 22 , wherein said ligand is transferrin.