Complexing agents for 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 an inclusion complex of a cyclodextrin-containing polymer and a compound of the formula:
wherein
Host/Guest is a guest moiety;
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 —Y)O—,
a peptide or polypeptide residue, or —NH—(C═O)—CH(R 1 )—NH—(C═O)—CH(R 1 )—NH—;
Y is an additional host-guest functionality;
R 1 is —(CH 2 )—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 —NH—, —NH—(C═O)—(CH 2 ) e —(C═O)—CH 2 —, —S(═O) 2 —HC═CH—, —SS—, —C(═O)O—, or a carbohydrate residue;
a is 0 or 1;
b is 0 or 1;
d ranges from 0 to 6;
e ranges from 1 to 6;
m is 1;
n ranges from 1 to 6;
q is 1;
w ranges from 1 to 5;
y is 1; and
x is 1.
2. The composition of claim 1 , wherein the host/guest is selected from adamantyl, naphthyl, cholesterol, and mixtures thereof.
3. The composition of claim 1 , wherein the compound has the formula:
wherein
J is a peptide or polypeptide residue.
4. The composition of claim 3 , wherein the host/guest is selected from adamantyl, naphthyl, cholesterol, and mixtures thereof.
5. The composition of claim 3 or 1 , wherein n is 1.
6. The composition of claim 1 , wherein the PEG moiety increases solubility and/or imparts stabilization of a composition comprising the compound, a cyclodextrin-containing polymer, and pGL3-CV plasmid relative to a composition comprising the cyclodextrin-containing polymer and the pGL3-CV plasmid without the compound.
7. The composition of claim 6 , wherein the increase in solubility or stabilization occurs under biological conditions.
8. The composition of claim 1 , wherein at least one Functional Group includes a therapeutic agent, a ligand, a nuclear localization signal, an endosomal release peptide, an endosomal release polymer, or a membrane permeabilization agent.
9. The composition of claim 8 , wherein at least one Functional Group includes a therapeutic agent.
10. The composition of claim 9 , wherein the therapeutic agent is selected from antibiotics, steroids, polynucleotides, small molecule pharmaceuticals, viruses, plasmids, peptides, peptide fragments, chelating agents, natural products, biologically active macromolecules, proteins, enzymes, and mixtures thereof.
11. The composition of claim 8 , wherein at least one Functional Group includes a ligand.
12. The composition of claim 11 , wherein the ligand is selected from vitamins, proteins, monoclonal antibodies, monosaccharides, peptides, and polysaccharides.
13. The composition of claim 1 , wherein at least one Functional Group includes a moiety that increases the solubility and/or imparts stabilization, under biological conditions, of a composition comprising the compound, a cyclodextrin-containing polymer, and pGL3-CV plasmid relative to a composition comprising the cyclodextrin-containing polymer and the pGL3-CV plasmid without the compound.
14. The composition of claim 1 , wherein a is 1.
15. The composition of claim 1 , wherein at least one Functional Group includes at least one polymer portion.
16. The composition of claim 12 , wherein the ligand is a protein.
17. The composition of claim 16 , wherein the protein is transferrin.
18. The composition of claim 1 , wherein the composition further comprises a therapeutic agent.
19. The composition of claim 18 , wherein the therapeutic agent is selected from antibiotics, steroids, polynucleotides, small molecule pharmaceuticals, viruses, plasmids, peptides, peptide fragments, chelating agents, natural products, biologically active macromolecules, proteins, enzymes, and mixtures thereof.
20. The composition of claim 19 , wherein the therapeutic agent is a polynucleotide.