Nucleic acid-small diameter and liquid core nanoparticle complexed compositions
The disclosure provides nanoemulsion compositions and methods of making and using thereof to deliver a bioactive agent such as a nucleic acid to a subject. The nanoemulsion composition comprises a hydrophobic core based on inorganic nanoparticles in a lipid nanoparticle that allows imaging as well as delivering nucleic acids. Methods of using these particles for treatment and vaccination are also provided.
1. A composition, wherein the composition comprises:
nucleic acids, wherein the nucleic acids comprise a sequence encoding for an antibody to an antigen; and
lipid nanoparticles, wherein the lipid nanoparticles are characterized as having a z-average diameter particle size measurement of about 20 nm to about 60 nm when measured using dynamic light scattering, and wherein the lipid nanoparticles comprise:
a surface comprising cationic lipids; and
a hydrophobic core, wherein the hydrophobic core comprises liquid oil, wherein lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius, and
wherein the nucleic acids are complexed to the cationic lipids to form nucleic acid-lipid nanoparticle complexes.
2. The composition of claim 1 , wherein the antigen is derived from a virus.
3. The composition of claim 2 , wherein the virus is an RNA virus.
4. The composition of claim 3 , wherein the RNA virus is a Human Immunodeficiency Virus (HIV) virus or a hepatitis virus.
5. The composition of claim 3 , wherein the RNA virus is a Coronavirus.
6. The composition of claim 5 , wherein the Coronavirus is a MERS Coronavirus or a SARS Coronavirus.
7. The composition of claim 5 , wherein the Coronavirus is SARS-COV-2 virus.
8. The composition of claim 3 , wherein the RNA virus is a mosquito-borne virus.
9. The composition of claim 8 , wherein the mosquito-borne virus is Venezuelan equine encephalitis (VEE) virus.
10. The composition of claim 8 , wherein the mosquito-borne virus is a flavivirus.
11. The composition of claim 10 , wherein the flavivirus is Zika Virus.
12. The composition of claim 1 , wherein the antigen is derived from a cancer.
13. The composition of claim 1 , wherein the antigen is derived from a bacterium.
14. The composition of claim 1 , wherein the lipid nanoparticles are characterized as having a z-average diameter particle size measurement of 40 nm to 60 nm when measured using dynamic light scattering.
15. The composition of claim 1 , wherein the surface further comprises a hydrophobic surfactant and a hydrophilic surfactant.
16. The composition of claim 15 , wherein the hydrophobic surfactant is selected from the group consisting of sorbitan monostearate, sorbitan monooleate, and sorbitan trioleate.
17. The composition of claim 15 , wherein the hydrophilic surfactant comprises polyethylene oxide.
18. The composition of claim 15 , wherein the hydrophilic surfactant comprises polysorbate.
19. The composition of claim 18 , wherein the polysorbate comprises polysorbate 80.
20. The composition of claim 1 , wherein the cationic lipids comprise 1,2-dioleoyloxy-3-(trimethylammonium)propane (DOTAP); 3b-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC Cholesterol); dimethyldioctadecylammonium (DDA); 1,2-dimyristoyl-3-trimethylammoniumpropane (DMTAP), dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP); distearoyltrimethylammonium propane (DSTAP); N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA); N,N-dioleoyl-N,N-dimethylammonium chloride (DODAC); 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC); 1,2-dioleoyl-3-dimethylammonium-propane (DODAP); 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA); or 1,r-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl) (2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol) (C 12-200).
21. The composition of claim 1 , wherein the cationic lipids are DOTAP.
22. The composition of claim 1 , wherein the hydrophobic core further comprises a solid inorganic nanoparticle.
23. The composition of claim 22 , wherein the solid inorganic nanoparticle is selected from the group consisting of metal salts, metal oxides, metal hydroxides, and metal phosphates.
24. The composition of claim 23 , wherein the solid inorganic nanoparticle comprises iron oxide.
25. The composition of claim 24 , wherein the iron oxide is magnetite (Fe 3 O 4 ), maghemite (y-Fe 2 O 3 ), wüstite (FeO), hematite (a-Fe 2 O 3 ), or any combination thereof.
26. The composition of claim 1 , wherein the liquid oil comprises vegetable oil, animal oil, or synthetically prepared oil.
27. The composition of claim 1 , wherein the liquid oil comprises squalene, sunflower oil, soybean oil, olive oil, grapeseed oil, capric/caprylic triglyceride, vitamin E, lauroyl polyoxylglyceride, or monoacylglycerol.
28. The composition of claim 1 , wherein the hydrophobic core further comprises iron oxide, wherein the surface further comprises sorbitan monostearate and polysorbate 80, wherein the liquid oil is squalene, and wherein the cationic lipid is DOTAP.
29. The composition of claim 1 , wherein the nucleic acids comprise RNA or DNA.
30. The composition of claim 1 , wherein the nucleic acids further comprise a sequence encoding for an RNA polymerase complex region from an RNA virus.
31. The composition of claim 30 , wherein the RNA polymerase complex region comprises sequence from a Venezuelan equine encephalitis virus.
32. The composition of claim 31 , wherein the Venezuelan equine encephalitis virus is strain TC-83.
33. The composition of claim 30 , wherein the RNA polymerase complex region comprises sequence encoding for nsP1-4.