Process for encapsulating soluble biologics, therapeutics, and imaging agents

1. A nanoparticle comprising:

a core comprising a more polar region of a linear copolymer and a water soluble agent,

a shell comprising a less polar region of the linear copolymer, and

a coating,

wherein the more polar region of the copolymer in the core is crosslinked through a crosslinking agent,

wherein the less polar region of the linear copolymer comprises poly(n-butyl acrylate) (PBA), poly(lactic acid) (PLA), poly(caprolactone) (PCL), poly(lactic-co-glycolic acid) (PLGA), or combinations,

wherein the coating comprises an inner region and an outer region,

wherein the inner region comprises a hydrophobic region of an amphiphilic polymer, and

wherein the outer region comprises a hydrophilic region of the amphiphilic polymer.

2. The nanoparticle of claim 1 , wherein the linear copolymer is a diblock copolymer.

3. The nanoparticle of claim 1 , wherein the linear copolymer consists of a hydrophilic block coupled with a hydrophobic block.

4. The nanoparticle of claim 1 , wherein the more polar region of the linear copolymer comprises an anionic more polar region.

5. The nanoparticle of claim 4 , wherein the anionic more polar region comprises a polymer selected from the group consisting of poly(acrylic acid) (PAA), hyaluronic acid, poly(glutamic acid), poly(aspartic acid), and combinations thereof.

6. The nanoparticle of claim 1 , wherein the more polar region of the linear copolymer comprises a cationic more polar region.

7. The nanoparticle of claim 6 , wherein the cationic more polar region comprises a polymer selected from the group consisting of chitosan, polyethylene-imines, and combinations thereof.

8. The nanoparticle of claim 1 , wherein the linear copolymer is poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PBA).

9. The nanoparticle of claim 1 , wherein the linear copolymer is biodegradable.

10. The nanoparticle of claim 1 ,

wherein the copolymer is a block copolymer,

wherein the more polar region of the copolymer consists of poly(glutamic acid) and/or poly(aspartic acid), and

wherein the less polar region of the copolymer consists of poly(lactic acid) (PLA) or poly(lactic-co-glycolic acid) (PLGA).

11. The nanoparticle of claim 1 , wherein the nanoparticle has an average size of at least 100 nm.

12. The nanoparticle of claim 1 , wherein the more polar region of the copolymer in the core is crosslinked through non-covalent crosslinks.

13. The nanoparticle of claim 1 , wherein the more polar region of the copolymer in the core is crosslinked through chelation crosslinks.

14. The nanoparticle of claim 1 , wherein the more polar region of the copolymer in the core is crosslinked through hydrogen bonding.

15. The nanoparticle of claim 1 ,

wherein the more polar region of the linear copolymer comprises a portion of anionic functionality and

wherein the crosslinking agent crosslinks the portion of anionic functionality of the more polar region of the linear copolymer.

16. The nanoparticle of claim 1 , wherein the crosslinking agent is selected from the group consisting of a metal salt, a metal halide, and an organometallic salt.

17. The nanoparticle of claim 1 , wherein the crosslinking agent is selected from the group consisting of an alkaline earth metal halide, a magnesium halide, magnesium chloride, a calcium halide, calcium chloride, a transition metal halide, an iron halide, a chromium halide, chromium(III) chloride, and chromium(III) bromide.

18. The nanoparticle of claim 1 , wherein the crosslinking agent is iron(III) chloride.

19. The nanoparticle of claim 1 , wherein the crosslinking agent is selected from the group consisting of a metal acetate, an alkaline earth acetate, calcium acetate, and a transition metal acetate.

20. The nanoparticle of claim 1 , wherein the crosslinking agent is chromium (III) acetate.

21. The nanoparticle of claim 1 , wherein the crosslinking agent is tobramycin.

22. The nanoparticle of claim 1 ,

wherein the more polar region of the linear copolymer comprises a portion of cationic functionality and

wherein the crosslinking agent crosslinks the portion of cationic functionality of the more polar region of the copolymer.

23. The nanoparticle of claim 22 , wherein the crosslinking agent is selected from the group consisting of polycitric acid, polyacrylic acid, polyaspartic acid, and polyglutamic acid.

24. The nanoparticle of claim 1 , wherein the water soluble agent is selected from the group consisting of a biologic material, an amino acid, a peptide, a protein, DNA, RNA, a saccharide, glutathione, tryptophan, a lysozyme, glucagon-like peptide-1 (GLP-1), a water soluble small molecule therapeutic, tobramycin, vancomycin, an imaging agent, eosin, eosin Y, tartrazine, a metal chelate, a gadolinium chelate, and gadolinium diethylene triamine pentaacetic acid (GD-DTPA).

25. The nanoparticle of claim 1 , wherein the amphiphilic polymer of the coating is selected from the group consisting of a block copolymer, a diblock copolymer, a triblock copolymer, and a multiblock copolymer.

26. The nanoparticle of claim 1 , wherein the amphiphilic polymer of the coating is selected from the group consisting of polystyrene-block-poly(ethylene glycol) (PS-b-PEG), poly(lactic acid)-block-poly(ethylene glycol) (PLA-b-PEG), poly(caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG), poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG), and poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO).

27. The nanoparticle of claim 1 , wherein the less polar region of the linear copolymer comprises poly(n-butyl acrylate) (PBA).

28. A nanoparticle comprising:

a core comprising a more polar region of a linear copolymer and a water soluble agent and

a shell comprising a less polar region of the linear copolymer,

wherein the more polar region of the copolymer in the core is crosslinked through a crosslinking agent and

wherein the crosslinking agent is tobramycin.