Targeted therapeutic nanoparticles and methods of making and using same
View Patent ↗Described herein are polymeric nanoparticles that include a therapeutic agent, and methods of making and using such therapeutic nanoparticles. In some embodiments, the contemplated nanoparticles may include an excipient.
1. A therapeutic nanoparticle comprising:
about 0.05 to about 30 weight percent of an excipient selected from the group consisting of a polyanionic polymer and a polycationic polymer;
about 0.2 to about 35 weight percent of a therapeutic agent;
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene)glycol copolymer; and
about 35 to about 99.75 weight percent of a biocompatible polymer.
2. The therapeutic nanoparticle of claim 1 , wherein the excipient is a polyanionic polymer, wherein the polyanionic polymer is a copolymer of methacrylic acid and methyl methacrylate subunits.
3. The therapeutic nanoparticle of claim 2 , wherein the ratio of methacrylic acid to methyl methacrylate subunits is between about 1:0.9 to about 1:3.
4. The therapeutic nanoparticle of claim 1 , wherein the excipient is a polycationic polymer, wherein the polycationic polymer is: i) a copolymer of alkyl methacrylate and dimethylaminoethylmethacrylate, or ii) a copolymer of dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate subunits.
5. The therapeutic nanoparticle of claim 4 , wherein the ratio of dimethylaminoethyl methacrylate to butyl methacrylate to methyl methacrylate subunits is about 1:2:1.
6. The therapeutic nanoparticle of claim 1 , wherein the excipient has a molecular weight of between about 20 kDa and about 60 kDa.
7. The therapeutic nanoparticle of claim 1 , wherein the excipient has a molecular weight of between about 100 kDa and about 150 kDa.
8. The therapeutic nanoparticle of claim 1 , further comprising about 0.05 to about 35 weight percent cyclodextrin, wherein the cyclodextrin is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and mixtures thereof.
9. The therapeutic nanoparticle of claim 8 , comprising about 15 to about 30 weight percent cyclodextrin.
10. The therapeutic nanoparticle of claim 1 , wherein the therapeutic agent is a chemotherapeutic agent.
11. The therapeutic nanoparticle of claim 1 , wherein the hydrodynamic diameter of the therapeutic nanoparticle is about 60 to about 200 nm.
12. The therapeutic nanoparticle of claim 1 , wherein the biocompatible polymer is selected from the group consisting of poly(lactic) acid-poly(ethylene)glycol copolymer and poly(lactic) acid-co-poly(glycolic) acid-poly(ethylene)glycol copolymer.
13. The therapeutic nanoparticle of claim 12 , wherein the poly(lactic) acid-poly(ethylene)glycol copolymer has a poly(lactic) acid number average molecular weight fraction of about 0.6 to about 0.95.
14. The therapeutic nanoparticle of claim 1 , wherein the therapeutic nanoparticle comprises about 10 to about 25 weight percent poly(ethylene)glycol.
15. The therapeutic nanoparticle of claim 1 , wherein the therapeutic nanoparticle comprises about 20 to about 30 weight percent poly(ethylene)glycol.
16. The therapeutic nanoparticle of claim 1 , wherein the nanoparticle substantially immediately releases less than about 70% of the therapeutic agent after 0.5 hours when placed in a phosphate buffer solution at 37° C.
17. A pharmaceutically acceptable composition comprising a plurality of therapeutic nanoparticles of claim 1 , and a pharmaceutically acceptable excipient.
18. The pharmaceutically acceptable composition of claim 17 , further comprising a saccharide and/or cyclodextrin.
19. The pharmaceutically acceptable composition of claim 18 , wherein the saccharide is a disaccharide selected from the group consisting of sucrose or trehalose, or a mixture thereof.
20. The pharmaceutically acceptable composition of claim 18 , wherein the cyclodextrin is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and mixtures thereof.