TARGETED DRUG DELIVERY AND THERAPEUTIC METHODS USING APO-E MODIFIED LIPID NANOPARTICLES
First Claim
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1. A method for enhancing transport of a therapeutic agent to a target cell or tissue, comprising:
- administering to a subject a lipid nanoparticle loaded with the therapeutic agent, the lipid nanoparticle comprising;
a lipid core comprised of a triglyceride component and a cholesterol ester component;
the therapeutic agent;
a phospholipid layer;
a surfactant coating layer surrounding the phospholipid layer and the lipid core; and
a human recombinant apolipoprotein (ApoE3) adsorbed to a surface of the nanoparticle without Polysorbate 80,wherein;
the lipid nanoparticle has preferential uptake in brain, lung, kidney and liver tissues that overexpress LDL receptors.
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Abstract
Methods for targeted delivery of therapeutic agents to a target cell or tissue with lipid nanoparticles comprising ApoE3. In embodiments, the invention specifically relates to targeted delivery of anticancer drugs, antibiotics, antifungal drugs, and diagnostic contrast agents, and associated treatment and diagnostic methods. In embodiments, diseases/conditions treated include those associated with over-expression of LDL receptors.
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Citations
22 Claims
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1. A method for enhancing transport of a therapeutic agent to a target cell or tissue, comprising:
administering to a subject a lipid nanoparticle loaded with the therapeutic agent, the lipid nanoparticle comprising; a lipid core comprised of a triglyceride component and a cholesterol ester component; the therapeutic agent; a phospholipid layer; a surfactant coating layer surrounding the phospholipid layer and the lipid core; and a human recombinant apolipoprotein (ApoE3) adsorbed to a surface of the nanoparticle without Polysorbate 80, wherein; the lipid nanoparticle has preferential uptake in brain, lung, kidney and liver tissues that overexpress LDL receptors. - View Dependent Claims (2, 3, 4)
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5. A method for enhancing transport of a therapeutic agent across a blood-brain barrier to a target cell or tissue, comprising:
administering to a subject a lipid nanoparticle loaded with the therapeutic agent, the lipid nanoparticle comprising; a lipid core comprised of a triglyceride component and a cholesterol ester component; the therapeutic agent; a phospholipid layer; a surfactant coating layer surrounding the phospholipid layer and the lipid core; and human recombinant apolipoprotein (ApoE3) adsorbed to a surface of the nanoparticle without Polysorbate 80, wherein; the therapeutic agent is transported to the target cell or tissue in a concentration that is at least 10 times greater than a concentration transported by the same lipid nanoparticle without human recombinant ApoE3 adsorbed thereto. - View Dependent Claims (6, 7, 8, 9, 10)
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11. A method of treating a disease associated with brain tissue, comprising:
administering a therapeutically effective amount of a therapeutic agent to an individual having the disease, the therapeutic agent being loaded onto lipid nanoparticles comprising; a lipid core comprised of a triglyceride component and a cholesterol ester component; a phospholipid layer; a surfactant coating surrounding the phospholipid and the lipid core; and a human recombinant apolipoprotein (ApoE3) adsorbed to a surface of the nanoparticle without Polysorbate 80, wherein the apolipoprotein is human recombinant ApoE3, wherein the therapeutic agent is transported in the lipid nanoparticle across the blood-brain barrier to the target brain tissue through transcytosis independent of LDL receptor binding. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18)
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19. A method for treating skin conditions associated with reduced collagen production, comprising:
topically applying a composition comprising a therapeutically effective amount of lipid nanoparticles to an affected area on a surface of the skin, the lipid nanoparticles comprising; a lipid core comprised of a triglyceride component and a cholesterol ester component; a phospholipid layer; a surfactant coating layer surrounding the phospholipid layer and the lipid core; a human recombinant apolipoprotein (ApoE3) bonded to a surface of the nanoparticle without Polysorbate 80; and at least one therapeutic agent in the lipid core, wherein the nanoparticles diffuse from the surface of the skin across the epidermis, resulting in the therapeutic agent being intracellularly released in the dermis by LDL receptor-mediated endocytosis and stimulating fibrobplast collagen production. - View Dependent Claims (20, 21)
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22. The method for treating skin conditions according to claim 22, wherein the therapeutic agent is Ingenol.
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