Compositions and methods for delivery of nucleic acid-lipid nanoparticle complexes encoding for viral RNA polymerase region and protein antigen
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. Compositions of the disclosure include nucleic-acid lipid nanoparticle complexes encoding for viral RNA polymerase region and protein antigen. The nanoemulsion compositions of the disclosure comprises a hydrophobic core, optionally including 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, including methods for administering to a subject a composition of the disclosure in an amount sufficient to generate an immune response.
1. A method comprising:
administering to a subject a composition in an amount sufficient to generate an immune response, wherein the composition comprises:
nanoparticles, wherein the nanoparticles comprise:
a hydrophobic core comprising a mixture of liquid oil and a solid inorganic nanoparticle;
a cationic lipid;
a hydrophilic surfactant; and
a hydrophobic surfactant; and
nucleic acids encoding for a protein antigen, wherein the nucleic acids are complexed with the nanoparticles to form nucleic acid-nanoparticle complexes.
2. The method of claim 1 , wherein the nucleic acids comprise RNA.
3. The method of claim 2 , wherein the RNA is mRNA.
4. The method of claim 3 , wherein the mRNA further comprises a sequence encoding for a Venezuelan equine encephalitis viral sequence.
5. The method of claim 1 , wherein administration of the composition is intramuscular, parenteral, or intradermal.
6. The method of claim 1 , wherein administration of the composition is intranasal.
7. The method of claim 1 wherein administration of the composition is by inhalation.
8. The method of claim 1 , wherein the hydrophobic core does not comprise glyceryl trimyristate.
9. The method of claim 1 , wherein the hydrophobic surfactant is selected from the group consisting of sorbitan monostearate, sorbitan monooleate, and sorbitan trioleate.
10. The method of claim 1 , wherein cationic lipid is selected from the group consisting of 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); and 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).
11. The method of claim 10 , wherein the cationic lipid is DOTAP.
12. The method of claim 1 , wherein the solid inorganic nanoparticle is selected from the group consisting of metal salts, metal oxides, metal hydroxides, and metal phosphates.
13. The method of claim 1 , wherein the solid inorganic nanoparticle comprises iron oxide.
14. The method of claim 13 , wherein the iron oxide is magnetite (Fe 3 O 4 ), maghemite (y-Fe 2 O 3 ), wustite (FeO), hematite (a-Fe 2 O 3 ), or any combination thereof.
15. The method of claim 1 , wherein the liquid oil is a vegetable oil, an animal oil or a synthetically prepared oil.
16. The method of claim 1 , wherein the liquid oil is capric/caprylic triglyceride, vitamin E, lauroyl polyoxylglyceride, monoacylglycerol, squalene, or any combination thereof.
17. The method of claim 1 , wherein the liquid oil is squalene, sunflower oil, soybean oil, olive oil, grapeseed oil, capric/caprylic triglyceride, or any combination thereof.
18. The method of claim 1 , wherein the liquid oil is squalene.
19. The method of claim 1 , wherein the hydrophilic surfactant comprises polyethylene oxide.
20. The method of claim 19 , wherein the polyethylene oxide comprises polyoxyethylene sorbitan ester.
21. The method of claim 1 , wherein the hydrophilic surfactant comprises polysorbate.
22. The method of claim 21 , wherein the polysorbate comprises polysorbate 80.
23. The method of claim 1 , wherein the liquid oil comprises squalene, wherein the solid inorganic nanoparticle comprises iron oxide, wherein the cationic lipid comprises DOTAP, wherein the hydrophobic surfactant comprises sorbitan monostearate, and wherein the hydrophilic surfactant comprises polysorbate 80.
24. The method of claim 1 , wherein the liquid oil is squalene, wherein the solid inorganic nanoparticle is iron oxide, wherein the cationic lipid is DOTAP, wherein the hydrophobic surfactant is sorbitan monostearate, and wherein the hydrophilic surfactant is polysorbate 80.
25. The method of claim 24 , wherein the composition further comprises sodium citrate.
26. The method of claim 1 , wherein the liquid oil comprises from about 2% to about 40% w/v squalene, wherein the solid inorganic nanoparticle comprises from about 0.001% to about 10% w/v iron oxide, wherein the cationic lipid comprises from about 0.2% to about 10% w/v DOTAP, wherein the hydrophobic surfactant comprises from about 0.25% to about 5% w/v sorbitan monostearate, and wherein the hydrophilic surfactant comprises from about 0.5% to about 10% w/v polysorbate 80.
27. The method of claim 1 , wherein the protein antigen is a bacterial, viral, protozoan, or cancer protein antigen.
28. The method of claim 1 , wherein the nucleic acids comprise DNA.