Lipid-polymer hybrid particles
A particle includes an aqueous core; a first amphiphilic layer surrounding the aqueous core; and a polymeric matrix surrounding the first amphiphilic layer.
1. A particle comprising:
an aqueous core;
a first amphiphilic layer surrounding the aqueous core;
a polymeric matrix surrounding the first amphiphilic layer; and
one or more active agents, wherein at least one of the active agents is an immunostimulatory agent comprising a toll receptor (TLR) ligand ss/dsRNA, a polyI:C polynucleotide, or a CpG polynucleotide.
2. The particle of claim 1 , further comprising a second amphiphilic layer surrounding the polymeric matrix.
3. The particle of claim 1 , wherein the particle has an average diameter between about 40 nm and about 400 μm.
4. The particle of claim 1 , wherein the first amphiphilic layer is a multilayer.
5. The particle of claim 1 , wherein the first amphiphilic layer comprises naturally derived lipids, surfactants, or synthesized compounds with both hydrophilic and hydrophobic moieties.
6. The particle of claim 1 , wherein the first amphiphilic layer comprises 1,2-dimyristoleoyl-sn-glycero-3-ethylphosphocholine (EPC14:1).
7. The particle of claim 1 , wherein the first amphiphilic layer has a thickness of about 1 nm to about 50 nm.
8. The particle of claim 1 , wherein the polymeric matrix comprises poly(lactide-co-glycolide) (PLGA), a polyalkylene glycol, or a polyester.
9. The particle of claim 1 , wherein the polymeric matrix comprises polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, or polyamines, or combinations thereof.
10. The particle of claim 8 , wherein the polyester is poly(lactide-co-glycolide) (PLGA), polylactic acid, or polycaprolactone.
11. The particle of claim 1 , wherein the polymeric matrix comprises a copolymer of two or more polymers.
12. The particle of claim 11 , wherein the copolymer is a copolymer of poly(lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG).
13. The particle of claim 1 , wherein the polymeric matrix comprises a lipid-terminated polyalkylene glycol and a polyester or a polyethylene glycol (PEG) and poly(lactide-co-glycolide) (PLGA).
14. The particle of claim 1 , wherein the polymeric matrix comprises a biodegradable polymer.
15. The particle of claim 2 , wherein the second amphiphilic layer is a multilayer.
16. The particle of claim 2 , wherein the second amphiphilic layer comprises lecithin.
17. The particle of claim 2 , wherein the second amphiphilic layer has a thickness of about 1 nm to about 50 nm.
18. The particle of claim 1 , further comprising a targeting agent.
19. The particle of claim 18 , further comprising a second amphiphilic layer surrounding the polymeric matrix, and wherein the targeting agent is conjugated to a hydrophilic region of a molecule of the second amphiphilic layer.
20. The particle of claim 18 , wherein the targeting agent comprises any one or more of a nucleic acid aptamer, polypeptide, protein ligand, small molecule, growth factor, hormone, cytokine, interleukin, antibody, antibody fragment, integrin, fibronectin receptor, carbohydrate, p-glycoprotein receptor, peptide, peptidomimetic, hydrocarbon, small modular immunopharmaceutical, cell binding sequence, affibody, nanobody, adnectin, domain antibody, or an avimer.
21. The particle of claim 1 , further comprising an antigen associated with a surface of the particle.
22. The particle of claim 21 , further comprising a second amphiphilic layer surrounding the polymeric matrix, and wherein the antigen is conjugated to a hydrophilic region of a molecule of the second amphiphilic layer.
23. The particle of claim 1 , wherein at least one of the one or more the active agents is a therapeutic agent, immunomodulatory agent, diagnostic agent, biomolecule, bioactive agent, small molecule, drug, prodrug, protein, polypeptide, immunogen, hapten, or adjuvant.
24. A composition comprising a plurality of particles described in claim 1 .
25. The composition of claim 24 , wherein the plurality of particles has an average characteristic dimension of 500 nm or less.
26. A particle comprising:
an aqueous core;
a first amphiphilic layer surrounding the aqueous core, wherein the first amphiphilic layer comprises 1,2-dimyristoleoyl-sn-glycero-3-ethylphosphocholine (EPC14:1); and
a polymeric matrix surrounding the first amphiphilic layer.
27. The particle of claim 26 , further comprising one or more active agents.
28. The particle of claim 27 , wherein at least one of the active agents is an immunostimulatory agent.
29. The particle of claim 28 , wherein the immunostimulatory agent is a toll receptor (TLR) ligand ss/dsRNA, polyI:C polynucleotide, or CpG polynucleotide.
30. The particle of claim 26 , wherein the polymeric matrix comprises poly(lactide-co-glycolide) (PLGA), a polyalkylene glycol, or a polyester.
31. The particle of claim 1 , wherein the immunostimulatory agent comprises a toll receptor (TLR) ligand ss/dsRNA.
32. The particle of claim 1 , wherein the immunostimulatory agent comprises a polyI:C polynucleotide.
33. The particle of claim 1 , wherein the immunostimulatory agent comprises a CpG polynucleotide.