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 amine-containing random copolymer, wherein said polymer comprises: plurality of first monomers each containing a pendant primary amine group, a plurality of second monomers each containing a pendant linear alkyl group having two to four carbon atoms, and a plurality of third monomers each containing a pendant linear alkyl group having eight or more carbon atoms wherein said random copolymer is capable of lysing red blood cells.
2. The membrane active random copolymer of claim 1 wherein the first pendant linear alkyl group consists of a butyl group.
3. The membrane active random copolymer of claim 1 wherein the second pendant linear alkyl group is selected from the group consisting of: dodecyl group, octadecyl group, and oleyl group.
4. The membrane active random copolymer of claim 1 wherein the random copolymer is soluble in aqueous solution.
5. The membrane active of claim 4 wherein the random copolymer is soluble in aqueous solution at 1 mg/ml or greater.
6. The membrane active random copolymer of claim 1 wherein the random copolymer is selected from the group consisting of: poly(acrylate), modified poly(alcohol), modified poly(amine), modified poly(allylamine), modified poly(vinyl amine), modified poly(amino acid), modified poly(β-aminoester) and poly(vinyl ether).
7. The membrane active random copolymer of claim 1 wherein the random copolymer is larger than about 5 kDa.
8. The membrane active random copolymer of claim 7 wherein the random copolymer is larger than about 7.5 kDa.
9. The membrane active random copolymer of claim 8 wherein the random copolymer is larger than about 10 kDa.
10. The membrane active random copolymer of claim 9 wherein the random copolymer is larger than about 15 kDa.
11. The membrane active random copolymer of claim 1 wherein the random copolymer is smaller than about 100 kDa.
12. The membrane active random copolymer of claim 11 wherein the random copolymer is smaller than about 50 kDa.
13. The membrane active random copolymer of claim 7 wherein the random copolymer is smaller than about 100 kDa.
14. The membrane active random copolymer of claim 13 wherein the random copolymer is smaller than about 50 kDa.
15. The membrane active random copolymer of claim 14 wherein the random copolymer is smaller than about 30 kDa.
16. The membrane active random copolymer of claim 1 wherein the primary amine-containing monomers contain of ethyl amines, propyl amines, or butyl amines.