Molecular-size of elastin-like polypeptide delivery system for therapeutics modulates intrarenal deposition and bioavailability
A renal cortex targeting elastin-like polypeptide (ELP), a renal medulla and cortex targeting ELP, and a method of treating a renal disorder are provided. The renal cortex targeting ELP includes up to 95 repeat units having the sequence VPGXG (SEQ ID NO: 1), where X in each of the repeat units is any amino acid except proline. The renal medulla and cortex targeting ELP includes at least 95 repeat units of SEQ ID NO: 1, where X in each of the repeat units is any amino acid except proline. The method of treating a renal disorder includes administering an ELP and a therapeutic drug to a subject in need thereof, where the ELP includes up to 671 repeat units of SEQ ID NO: 1 and X in each of the repeat units is any amino acid except proline.
1. A method of treating a renal disorder, the method comprising:
administering an elastin-like peptide (ELP) and a therapeutic drug to a subject in need thereof;
wherein the ELP includes at least 5 and up to 671 repeat units having the sequence VPGXG (SEQ ID NO: 1); and wherein X in each of the repeat units is individually selected from the group consisting of any amino acid except proline.
2. The method of claim 1 , wherein the ELP includes up to 95 of the repeat units.
3. The method of claim 1 , wherein the ELP includes at least 95 of the repeat units.
4. The method of claim 2 , wherein the ELP comprises between 5 and 95 of the repeat units.
5. The method of claim 2 , wherein the ELP comprises between 31 and 95 of the repeat units.
6. The method of claim 2 , wherein the ELP comprises between 63 and 95 of the repeat units.
7. The method of claim 2 , wherein the ELP comprises a molecular weight of up to 38 kDa.
8. The method of claim 2 , wherein the ELP comprises a molecular weight of between 13 kDa and 38 kDa.
9. The method of claim 2 , wherein the repeat units include V:G:A in a 1:4:3 ratio.
10. The method of claim 2 , wherein the ELP further comprises one or more of a therapeutic agent or agents, a drug binding domain, a targeting domain, or a cell penetrating peptide.
11. The method of claim 2 , wherein the ELP targets the renal cortex.
12. The method of claim 3 , wherein the ELP comprises between 95 and 671 of the repeat units.
13. The method of claim 3 , wherein the ELP comprises between 95 and 450 of the repeat units.
14. The method of claim 3 , wherein the ELP comprises between 95 and 287 of the repeat units.
15. The method of claim 3 , wherein the ELP comprises a molecular weight of at least 38 kDa.
16. The method of claim 3 , wherein the ELP comprises a molecular weight of between 38 kDa and 257 kDa.
17. The method of claim 3 , wherein the repeat units include V:G:A in a 1:4:3 ratio.
18. The method of claim 3 , wherein the ELP further comprises one or more of a therapeutic agent or agents, a drug binding domain, a targeting domain, or a cell penetrating peptide.
19. The method of claim 3 , wherein the ELP targets the renal medulla and cortex.
20. The method of claim 3 , wherein the renal disorder comprises renovascular disease or renal cancer.