Lipid-based nanoparticles and methods using same

A composition comprising a lipid-based nanoparticle,

• wherein the nanoparticle is enclosed by a bipolar lipid membrane comprising cholesterol, dicetyl phosphate, an amphipathic lipid, stearoyl lysophosphatidylcholine, and a hepatocyte receptor binding molecule;
• wherein the membrane comprises the cholesterol, dicetyl phosphate, amphipathic lipid, stearoyl lysophosphatidylcholine, and hepatocyte receptor binding molecule in a % (w/w) ratio such that:
• the cholesterol ranges from about 5% to about 15% (w/w),
• the dicetyl phosphate ranges from about 10% to about 25% (w/w),
• the hepatocyte receptor binding molecule ranges from about 0.5% to about 4% (w/w), and
• the stearoyl lysophosphatidylcholine ranges from about 1% to about 30% (w/w);
• wherein the amphipathic lipid comprises at least one selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycerol)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl), 1,2-dimyristoyl-sn-glycero-3-phosphate, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphate, 1,2-dipalmitoyl-sn-glycero-3-phosphate, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine;
• wherein the at least one hepatocyte receptor binding molecule extends outward from the nanoparticle;
• and
• wherein the size of the nanoparticle ranges from about 10 nm to about 150 nm.

A method of preparing a lipid-based nanoparticle, wherein the nanoparticle is enclosed by a bipolar lipid membrane, which comprises cholesterol, dicetyl phosphate, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), stearoyl lysophosphatidylcholine, and 2,3-diacetoxypropyl 2-(5-((3aS,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido) ethyl phosphate (biotin DHPE);

• wherein the membrane comprises cholesterol, dicetyl phosphate, DSPC, stearoyl lysophosphatidylcholine, and biotin DHPE in a % (w/w) ratio selected from the group consisting of:
• (a) about 9.4:18.1:56.8:14.1:1.5, and
• (b) about 8.4:16.2:47.5:7.6:1.3;
• wherein the biotin-DHPE extends outward from the nanoparticle;
• and
• wherein the size of the nanoparticle ranges from about 10 nm to about 150 nm, the method comprising contacting in an aqueous system cholesterol, dicetyl phosphate, DSPC, biotin-DHPE, and stearoyl lysophosphatidylcholine.

A method of preparing a lipid-based nanoparticle, wherein the nanoparticle is enclosed by a bipolar lipid membrane comprising cholesterol, dicetyl phosphate, an amphipathic lipid, stearoyl lysophosphatidylcholine, and a hepatocyte receptor binding molecule;

• wherein the membrane comprises the cholesterol, dicetyl phosphate, amphipathic lipid, stearoyl lysophosphatidylcholine, and hepatocyte receptor binding molecule in a % (w/w) ratio such that:
• the cholesterol ranges from about 5% to about 15% (w/w);
• the dicetyl phosphate ranges from about 10% to about 25% (w/w);
• the hepatocyte receptor binding molecule ranges from about 0.5% to about 4% (w/w);
• the stearoyl lysophosphatidylcholine ranges from about 1% to about 30% (w/w);
• wherein the amphipathic lipid comprises at least one selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycerol)], 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl), 1,2-dimyristoyl-sn-glycero-3-phosphate, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphate, 1,2-dipalmitoyl-sn-glycero-3-phosphate, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine;
• wherein the at least one hepatocyte receptor binding molecule extends outward from the nanoparticle;
• and
• wherein the size of the nanoparticle ranges from about 10 nm to about 150 nm, the method comprising contacting in an aqueous system cholesterol, dicetyl phosphate, amphipathic lipid, hepatocyte receptor binding molecule, and stearoyl lysophosphatidylcholine.