Nanoparticle complexes of paclitaxel, cetuximab, and albumin
Described are nanoparticle complexes comprising paclitaxel, albumin and anti-EGFR antibodies. The nanoparticle complexes are suitable for the treatment of cancer, in particular cancer that expresses EGFR.
1. An antibody-albumin nanoparticle complex comprising albumin, a cetuximab antibody, and paclitaxel, wherein the nanoparticle complex has been pre-formed in vitro by mixing an aqueous albumin-paclitaxel nanoparticle with the antibody under conditions to form the nanoparticle complex, such that the nanoparticle complex has EGFR binding specificity, wherein the complex has a diameter of about 0.1 μm to about 1 μm.
2. The antibody-albumin nanoparticle complex of claim 1 , further comprising an alkylating, agent.
3. The antibody-albumin nanoparticle complex of clam 2 , wherein said alkyating agent is a platinum compound.
4. The antibody-albumin nanoparticle complex of claim 3 , wherein said platinum compound is carboplatin.
5. The antibody-albumin nanoparticle complex of claim 1 , said complex having a diameter of between about 0.1 μm and about 0.9 μm.
6. The antibody-albumin nanoparticle complex of claim 1 , said complex having a diameter of between about 0.1 μm and about 0.3 μm.
7. The antibody-albumin nanoparticle complex of claim 1 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 5:1 and 1:2.5.
8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and antibody-albumin nanoparticle complexes, wherein said antibody-albumin complexes comprise albumin, a cetuximab antibody, and paclitaxel, wherein the nanoparticle complexes have been pre-formed in vitro by mixing an aqueous albumin-paclitaxel nanoparticles with the antibody under conditions to form the nanoparticle complexes, such that the nanoparticle complexes have EGFR binding specificity, wherein the average diameter of at least 90 percent of said complexes is between 0.1 μm and 0.95 μm.
9. The pharmaceutical composition of claim 8 , wherein said composition or said nanoparticle complexes comprise an alkylating agent.
10. The pharmaceutical composition of claim 9 , wherein said alkylating agent is a platinum compound.
11. The pharmaceutical composition of claim 10 , wherein said platinum compound is carboplatin.
12. The pharmaceutical composition of claim 8 , wherein the average diameter of said complexes is between 0.1 μm and 0.9 μm.
13. The pharmaceutical composition of claim 8 , wherein the average diameter of said complexes is between 0.1 μm and 0.3 μm.
14. The antibody-albumin nanoparticle complex of claim 8 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 5:1 and 1:2.5.
15. The pharmaceutical composition of claim 8 which is formulated for injection.
16. The pharmaceutical composition of claim 8 , wherein the pharmaceutically acceptable carrier is saline, water, lactic acid, mannitol, or a combination thereof.
17. A method of making an antibody-albumin nanoparticle complex, the method comprising mixing in vitro an aqueous albumin-paclitaxel nanoparticle with a cetuximab antibody under conditions to form the nanoparticle complex, wherein the complex has a diameter of about 0.1 μm to about 1 μm.