Lipid construct for delivery of insulin to a mammal

A method of increasing the bioavailability of at least one insulin in a patient, the method comprising:

• a. combining at least one insulin with a lipid-based particle to form a construct comprising the at least one insulin,
• wherein the lipid-based particle is defined by a bipolar lipid membrane comprising lipids comprising cholesterol, dicetyl phosphate, and an amphipathic lipid, and wherein the bipolar lipid membrane further comprises a hepatocyte receptor binding molecule,
• wherein the amphipathic lipid is at least one selected from the group consisting of 1,2-di stearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycero)], 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 hepatocyte receptor binding molecule is the only hepatocyte receptor binder in the composition and is a biotin-containing compound selected from the group consisting of biotin DHPE (2,3-diacetoxypropyl 2-(5-((3aS,6aR)-2-oxohexahydro-1H-thieno[3,4-d] imidazol-4-yl)pentanamido)ethyl phosphate), biotin-X-DHPE (2,3-diacetoxypropyl 2-(6-(5-((3aS,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanamido) ethyl phosphate), and any combinations thereof;
• wherein the biotin-containing compound extends outward from the lipid-based particle and binds to a biotin-binding hepatocyte receptor;
• and,
• wherein the size of the lipid-based particle ranges from 0.0200 to 0.40 μm;
• and
• b. administering the construct containing the at least one insulin to the patient.

A method of forming a time-release composition that provides increased biodistribution of insulin in a warm-bloodied subject, the method comprising:

• a. contacting (i) a bulk phase medium comprising an insulin-containing construct and (ii) streptavidin agarose affinity-gel, in a system of pH equal to or greater than about 9.5,
• wherein the construct comprises insulin and a lipid-based particle defined by a bipolar lipid membrane comprising lipids comprising cholesterol, dicetyl phosphate, and an amphipathic lipid,
• wherein the amphipathic lipid is at least one selected from the group consisting of 1,2-di stearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycerol-[3-phospho-rac-(1-glycero)], 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 at least one of the lipids comprises iminobiotin or an iminobiotin derivative,
• wherein the at least one lipid comprising iminobiotin or an iminobiotin derivative extends outward from the lipid-based particle,
• wherein the size of the lipid-based particle ranges from 0.0200 to 0.40 μm,
• whereby the insulin-containing construct binds to the affinity-gel;
• b. separating the construct-bound affinity-gel from the bulk phase medium;
• and
• c. subjecting the construct-bound affinity-gel to a system of pH of around 4.5,
• whereby the insulin-containing construct is released from the affinity-gel, wherein the released construct contains insoluble insulin.