Bioactive agent delivery particles
View Patent ↗The invention provides compositions and methods for delivery of a bioactive agent to an individual. Delivery vehicles are provided that include a bioactive agent in disc shaped particles that include one or more lipid binding polypeptides circumscribing the perimeter of a lipid bilayer in which the bioactive agent is localized. Chimeric lipid binding polypeptides are also provided and may be used to add additional functional properties to the delivery particles.
1. A bioactive agent delivery particle comprising a lipid binding polypeptide, a lipid bilayer, and wherein the lipid bilayer includes a lipid with one or more bound bioactive agents,
wherein the interior of the lipid bilayer comprises a hydrophobic region and the lipid is incorporated into the hydrophobic region of the lipid bilayer, and
wherein the particle does not comprise an aqueous core,
wherein the particle is disc-shaped with a discoidal lipid bilayer circumscribed by amphipathic α-helices and/or β sheets of the lipid binding polypeptide, which are associated with hydrophobic surfaces of the bilayer around the periphery of the particle; and
wherein the particle remains disc-shaped in aqueous solution.
2. The bioactive agent delivery particle according to claim 1 , wherein the lipid binding polypeptide further comprises a functional moiety.
3. The bioactive claim 2 , wherein the functional moiety is selected from the group consisting of a targeting moiety, affinity tag and reporter molecule.
4. The bioactive agent of claim 2 , wherein the functional moiety has biological activity.
5. The bioactive agent delivery particle according to claim 1 , wherein the lipid binding polypeptide is an apolipoprotein.
6. The bioactive agent delivery particle according to claim 5 , wherein the apolipoprotein is an exchangeable apolipoprotein, apolipoprotein E or is human apolipoprotein A-I.
7. The bioactive agent delivery particle according to claim 5 , wherein the apolipoprotein has been modified to increase stability of the particle.
8. The bioactive agent delivery particle according to claim 7 , wherein the modification comprises introduction of cysteine residues to form intermolecular or intramolecular disulfide bonds.
9. The bioactive agent delivery particle according to claim 1 , wherein the lipid bilayer comprises phospholipids.
10. The bioactive agent delivery particle according to claim 9 , wherein the phospholipids comprise dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidylcholine (DPPC) or egg phosphatidylcholine.
11. The bioactive agent delivery particle according to claim 1 , wherein the lipid binding polypeptide is an apolipoprotein selected from the group consisting of ApoA-I, apolipoprotein E (ApoE), and apolipophorin III (ApoIII), apolipoprotein A-IV (ApoA-IV), apolipoprotein A-V (ApoA-V), apolipoprotein C-I (ApoC-I), apolipoprotein C-II (ApoC-II), apolipoprotein C-III (ApoC-III), apolipoprotein D (ApoD), apolipoprotein A-II (ApoA-II), apolipoprotein B-100 (ApoB-100), apolipoprotein J (ApoJ), and apolipoprotein H (ApoH), or fragments, natural variants, isoforms, analogs, or chimeric forms thereof.
12. The bioactive agent delivery particle according to claim 1 , wherein the lipid binding polypeptide is an amphipathic peptide.
13. The bioactive agent delivery particle according to claim 5 , wherein the apolipoprotein is the N-terminal domain of apolipoprotein E3 or isoform thereof.
14. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is selected from antimicrobials, anticancer agents, pesticides, insecticides, herbicides, radiolabels, fluorescent compounds, anesthetics, bioactive lipids, anti-inflammatory agents, nutrients, lipopolysaccharides and photosensitizing agents used in photodynamic therapy.
15. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is a non-polypeptide.
16. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is an antimicrobial, a pesticide, or a herbicide.
17. The bioactive agent delivery particle according to claim 16 , wherein the antimicrobial is an antifungal.
18. The bioactive agent delivery particle according to claim 14 , wherein the bioactive agent is an insecticide.
19. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is an anticancer agent.
20. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent comprises all-trans retinoic acid, or Vitamin E.
21. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is selected from the group consisting of cell receptor proteins, enzymes, hormones and neurotransmitters.
22. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is a peptide.
23. The bioactive agent delivery particle according to claim 1 , wherein the particle further comprises an additional bioactive agent comprising at least one hydrophobic region incorporated into the hydrophobic region of the lipid bilayer.
24. A composition for delivery of a bioactive agent to an individual, comprising a bioactive agent delivery particle according to claim 1 and a carrier.
25. The composition of claim 24 , wherein the carrier is a pharmaceutically acceptable carrier.
26. The composition according to claim 24 , wherein the composition is formulated for controlled release, for topical administration or for parenteral administration.
27. The composition according to claim 26 , wherein said parenteral administration is selected from intravenous, intramuscular, transdermal, subcutaneous, intraperitoneal, transmucosal, and intrathecal.
28. The composition according to claim 24 , wherein the composition is formulated for aerosol delivery.
29. A kit comprising a pharmaceutical composition according to claim 24 and instructions for use in a method for administering a bioactive agent to an individual.
30. A method for administering a bioactive agent to an individual, comprising administering the composition of claim 24 to the individual.
31. The method according to claim 30 , wherein the individual is a plant.
32. The method according to claim 30 , wherein the individual is a vertebrate.
33. The bioactive agent delivery particle according to claim 1 , wherein the lipid with one or more bound bioactive agents is dipalmitoylphosphatidylserine (DPPS).
34. The bioactive agent delivery particle according to claim 1 , wherein the lipid with one or more bound bioactive agents is a ganglioside lipid.
35. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is a protein.
36. The bioactive agent delivery particle according to claim 1 , wherein the bioactive agent is an antigen.