Membrane active heteropolymers
View Patent ↗The present invention is directed to a class of membrane active polymers useful for cellular delivery of compounds. Conjugation of the described membrane active polymers to targeting, anti-opsonization, and anti-aggregation agents provides polymers suitable for in vivo delivery. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.
1. A membrane active polyamine formed by the process comprising: polymerizing via chain polymerization a plurality of input first monomers each containing a pendent protected amine, a plurality of input second monomers each containing a first hydrophobic pendent group having two to six carbon atoms, and a plurality of input third monomers each containing a second hydrophobic pendent group having twelve to twenty-two carbon atoms, thereby forming an amphipathic random heteropolymer and deprotecting the protected amines thereby forming the membrane active polyamine, wherein the ratio of input monomers is selected such that the membrane active polyamine contains a ratio of first monomers to second monomers to third monomers is about 6:3:1.
2. The membrane active polyamine of claim 1 wherein said first and second hydrophobic pendent groups are selected from the list consisting of: alkyl group, alkenyl group, alkynyl group, aryl group, aralkyl group, aralkenyl group, and aralkynyl group, each of which may be linear, branched, or cyclic and may can contain one or more substitutions or heteroatoms.
3. The membrane active polyamine of claim 1 wherein said first hydrophobic pendent group consists of a butyl group and said second hydrophobic groups consists of an octadecyl group.
4. The membrane active polyamine of claim 1 wherein the polyamine is soluble in aqueous solution.
5. The membrane active polyamine of claim 1 wherein the polyamine is soluble in aqueous solution at 1 mg/ml or greater.
6. The membrane active polyamine of claim 1 wherein the polyamine is selected from the group consisting of: poly(acrylate) and poly(vinyl ether).
7. The membrane active polyamine of claim 1 wherein the polyamine is biodegradable.
8. The membrane active polyamine of claim 7 wherein the polyamine contains biodegradable bonds within the backbone of the heteropolymer.
9. The membrane active polyamine of claim 7 wherein the polyamine contains biodegradable bonds within sidechains of the polyamine
10. The membrane active polyamine of claim 1 wherein the polyamine is larger than about 5 kDa.
11. The membrane active polyamine of claim 10 wherein the polyamine is larger than about 7.5 kDa.
12. The membrane active polyamine of claim 11 wherein the polyamine is larger than about 10 kDa.
13. The membrane active polyamine of claim 12 wherein the polyamine is larger than about 15 kDa.
14. The membrane active polyamine of claim 1 wherein the polyamine is smaller than about 100 kDa.
15. The membrane active polyamine of claim 14 wherein the polyamine is smaller than about 50 kDa.
16. The membrane active polyamine of claim 10 wherein the polyamine is smaller than about 100 kDa.
17. The membrane active polyamine of claim 11 wherein the polyamine is smaller than about 50 kDa.
18. The membrane active polyamine of claim 12 wherein the polyamine is smaller than about 30 kDa.
19. The membrane active polyamine of claim 1 wherein the amine-containing monomers contain of ethyl amines, propyl amines, or butyl amines
20. The membrane active polyamine of claim 1 wherein one of more targeting groups are covalently linked to the polyamine.
21. The membrane active polyamine of claim 20 wherein said targeting group is linked to the polymer via a physiologically labile bond.