Therapeutic particles suitable for parenteral administration and methods of making and using same
View Patent ↗Disclosed herein are therapeutic compositions for treating and preventing diseases such as neointimal hyperplasia (NIH), where the compositions comprise a therapeutic particle that has a localized association with a blood vessel and a therapeutic agent, such as an anti-NIH agent. Methods of use of the therapeutic compositions are also disclosed.
1. A method for decreasing the rate of neointimal hyperplasia (NIH) formation in a blood vessel of a patient receiving a bare metal stent in a lesion of said blood vessel, comprising:
administering a composition comprising therapeutic particles, wherein said therapeutic particles comprise:
about 1 to about 20 mole percent PLA-PEG-basement vascular membrane targeting peptide, wherein the targeting peptide comprises PLA having a number average molecular weight of about 15 to about 20 kDa and PEG having a number average molecular weight of about 4 to about 6 kDa;
about 10 to about 25 weight percent anti-neointimal hyperplasia (NIH) agent;
about 50 to about 90 weight percent non-targeted poly-lactic acid-PEG, wherein the therapeutic particles are capable of releasing the anti-NIH agent to a basement vascular membrane of a blood vessel for at least about 8 hours when the therapeutic particles are placed in the blood vessel.
2. The method of claim 1 , wherein the method provides a decreased or substantially comparable NIH rate at about 2 weeks after receiving said bare metal stent as compared to a patient receiving a stent comprising an anti-NIH agent at about 2 weeks.
3. The method of claim 1 , wherein the composition is administered using a catheter.
4. The method of claim 1 , wherein the composition is administered intravenously.
5. The method of claim 1 , wherein the composition is administered substantially simultaneously when the patient receives the stent.
6. The method of claim 1 , wherein the composition is administered before the patient receives the stent.
7. The method of claim 6 , wherein the composition is administered before a balloon catheter is introduced into the blood vessel.
8. The method of claim 6 , wherein the composition is administered after a balloon catheter is introduced into the blood vessel.
9. The method of claim 1 , wherein the basement vascular membrane targeting peptide comprises a sequence selected from the group consisting of AKERC (SEQ ID NO: 3), CREKA (SEQ ID NO: 1), ARYLQKLN (SEQ ID NO: 4), and AXYLZZLN (SEQ ID NO: 5), wherein X and Z are variable amino acids.
10. The method of claim 9 , wherein the basement vascular membrane targeting peptide comprises a sequence selected from the group consisting of AKERC (SEQ ID NO: 3) and CREKA (SEQ ID NO: 1).
11. The method of claim 1 , wherein the basement vascular membrane targeting peptide comprises a sequence selected from the group consisting of CREKA (SEQ ID NO: 1) and CARLYQKLN (SEQ ID NO: 2).
12. The method of claim 1 , wherein the non-targeted poly-lactic acid-PEG has PLA with a number average molecular weight of about 20 kDa to about 25 kDa.
13. The method of claim 1 , wherein the anti-neointimal hyperplasia (NIH) agent is paclitaxel.