Therapeutic particles suitable for parenteral administration and methods of making and using same
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 therapeutic particle comprising:
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; and
about 50 to about 90 weight percent non-targeted poly-lactic acid-PEG, wherein the therapeutic particle is 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 particle is placed in the blood vessel.
2. The therapeutic particle 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.
3. The therapeutic particle of claim 2 , wherein the basement vascular membrane targeting peptide is selected from: CREKA (SEQ ID NO: 1) or CARLYQKLN (SEQ ID NO: 2).
4. The therapeutic particle of claim 3 , wherein the anti-neointimal hyperplasia (NIH) agent is paclitaxel.