Temperature- and pH-responsive polymer compositions
Temperature- and pH-responsive copolymer compositions, and drug delivery devices, conjugates, nanoparticles, and micelles that include the compositions.
1. A block copolymer, comprising:
(a) a first block comprising a random copolymer comprising:
(i) temperature-responsive repeating units, wherein the repeating unit is an N-alkylacrylamide repeating unit; and
(ii) pH-responsive repeating units, wherein the repeating unit is a C2-C8 alkylacrylic acid repeating unit; and
(b) a second hydrophobic block.
2. The copolymer of claim 1 , wherein the copolymer exhibits a phase transition at a pH of from about pH 5.0 to about pH 7.4.
3. The copolymer of claim 1 , wherein the N-alkylacrylamide is a C3-C8 alkyl N-alkylacrylamide.
4. The copolymer of claim 1 , wherein the N-alkylacrylamide is N-isopropylacrylamide.
5. The copolymer of claim 1 , wherein the C2-C8 alkylacrylic acid is a C2-C8 n-alkylacrylic acid.
6. The copolymer of claim 1 , wherein the C2-C8 alkylacrylic acid is selected from the group consisting of ethylacrylic acid, n-propylacrylic acid, and n-butylacrylic acid.
7. The copolymer of claim 1 , wherein the C2-C8 alkylacrylic acid is n-propylacrylic acid.
8. The copolymer of claim 1 , wherein the pH-responsive repeating units are present in the random copolymer in an amount from about 1 to about 20 weight percent.
9. The copolymer of claim 1 , wherein the N-alkylacrylamide repeating unit is N-isopropylacrylamide and the alkylacrylic acid is propylacrylic acid.
10. The copolymer of claim 1 , wherein the random copolymer has a molecular weight of from about 5,000 to about 20,000.
11. The copolymer of claim 1 , wherein the block copolymer has a molecular weight of from about 15,000 to about 60,000.
12. The copolymer of claim 1 , wherein the hydrophobic block is selected from the group consisting of a polystyrene, a poly(methylmethacrylate), a poly(ethylacrylate), a poly(butylacrylate), a poly(glycotide-co-lactide), and a polyoxyethylene-polyoxypropylene copolymer.
13. The copolymer of claim 1 , wherein the hydrophobic block is selected from the group consisting of a poly(ethylacrylate) and a poly(butylacrylate).
14. A drug delivery device, comprising the copolymer of claim 1 and a therapeutic drug or diagnostic agent.
15. A conjugate, comprising the copolymer of claim 1 and a therapeutic drug or diagnostic agent.
16. A modified nanoparticle, comprising the copolymer of claim 1 attached to a nanoparticle.
17. The modified nanoparticle of claim 16 further comprising a therapeutic drug or diagnostic agent.
18. A micelle, comprising the copolymer of claim 1 and a therapeutic drug or diagnostic agent.