Hydrophobic core carrier compositions for delivery of therapeutic agents, methods of making and using the same

• US 9,737,615 B2
• Filed: 11/22/2013
• Issued: 08/22/2017
• Est. Priority Date: 12/19/2005
• Status: Active Grant

• Current Assignee: Pharmain Corporation
• Original Assignee: Pharmain Corporation
• Inventors: Castillo, Gerardo M., Bolotin, Elijah M.
• Primary Examiner(s): STANFIELD, CHERIE MICHELLE
• Application Number:
  US14/087,523
• Publication Number:
  US 20140154203A1
• Time in Patent Office: 1,369 Days
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 38/1808 Epidermal growth factor [EGF] urogastrone
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

The present invention relates, in part, to a biocompatible hydrophobic-core carrier comprising a carrier, and a plurality of hydrophobic groups covalently linked to the polymeric carrier. The hydrophobic groups are capable of dissociably linking load molecules such as therapeutic agents. The hydrophobic-core carrier may also comprise protective side chains, orienting molecules, and targeting molecules.

Claims

1. A composition, consisting of:

(i) a polymeric carrier; and

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein the hydrophobic group has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

2. The composition of claim 1, wherein the alkoxy derivative is methoxypolyethylene glycol, methoxypolypropylene glycol, or a methoxylated co-polymer of polyethylene glycol and polypropyleneglycol.

3. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein the first hydrophobic group has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain; and

(iii) a load molecule dissociably linked to the hydrophobic groups,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

4. The composition of claim 3, wherein the load molecule is a therapeutic agent.

5. The composition of claim 4, wherein the therapeutic agent is selected from the group consisting of glucagon-like-peptide, Gastric inhibitory polypeptide (GIP), Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, interferon, tumor necrosis factor, insulin, insulin-like growth factor, growth hormone, nerve growth factor, brain-derived neurotrophic factor, endostatin, angiostatin, thrombospondin, blood clotting factor VII, blood clotting factor VIII, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), thrombopoietin, calcitonin, parathyroid hormone (PTH), erythropoietin, atrial natriuretic factor, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, vasopressin, terlipressin, desmopressin, vasoactive intestinal peptide (VIP), anti-bacterial agents, anti-fungal agents, anti-viral agents, and vitamins.

6. The composition of claim 4, wherein the therapeutic agent is glucagon-like-peptide, Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, interferon, factor VIII, terlipressin, Gastric inhibitory polypeptide (GIP), vasoactive intestinal peptide (VIP) or nisin.

7. The composition of claim 4, wherein the therapeutic agent is glucagon-like-peptide, Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, or atrial natriuretic factor.

35. A method of treating diabetes in mammals, comprising administering a therapeutically effective amount of a composition of claim 7, wherein the therapeutic agent is selected from the group consisting of glucagon-like-peptide, Epidermal Growth Factor (EGF) receptor ligand, and Gastrin.

36. The method of claim 35 further comprising administering a therapeutically effective amount of a proton-pump inhibitor or a DPP4 inhibitor.

37. The method of claim 36, wherein the proton-pump inhibitor is omeprazole.

8. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein each hydrophobic group of the plurality of hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain; and

(iii) an orienting molecule covalently linked to the carrier, wherein the orienting molecule is selected from the group consisting of sulfate, sulfonate, phosphate, phosphonate, bisphosphonate, lysine, and arginine,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

9. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein each hydrophobic group of the plurality of hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) an orienting molecule covalently linked to the carrier, wherein the orienting molecule is selected from the group consisting of sulfate, sulfonate, phosphate, phosphonate, bisphosphonate, lysine, and arginine; and

(iv) a load molecule dissociably linked to the hydrophobic groups and/or the orienting molecule,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

10. A composition, consisting of:

(i) a polymeric carrier; and

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein each hydrophobic group of the plurality of the hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain; and

(iii) a targeting molecule covalently linked to the protective side chain, wherein the targeting molecule is selected from the group consisting of monocyte chemotactic protein 1, N-formyl-methionyl-leucyl-phenylalanine, granulocyte macrophage colony-stimulating factor (GM-CSF), colony stimulating factor-1, granulocyte macrophage colony-stimulating factor (GM-CSF) receptors, granulocyte macrophage colony-stimulating factor (GM-CSF) antibodies, colony stimulating factor-1 receptors, colony stimulating factor-1 antibodies, platelet factor 4;

TGF-fl growth factor, VEGF growth factor, E-selectin, VCAM-1 adhesive cell-surface glycoprotein, VCAM1f1 adhesive cell-surface glycoprotein, 11C-deoxy-D-glucose, C1 component of vascular inflammatory response, C1q component of vascular inflammatory response, C1r component of vascular inflammatory response, C1s component of vascular inflammatory response, C2 component of vascular inflammatory response, C3 component of vascular inflammatory response, C3a component of vascular inflammatory response, C3b component of vascular inflammatory response, C4 component of vascular inflammatory response, C4C2 component of vascular inflammatory response, C4C2C3b component of vascular inflammatory response, C5a component of vascular inflammatory response, C5b component of vascular inflammatory response, C5a component of vascular inflammatory response, interleukin 1, interleukin 10, interleukin 2, interleukin 3, interleukin 6, interleukin 7, interleukin 8, interferon α

, interferon γ

, tumor necrosis factor TNF-α

, polyethylene glycol coated liposomes, cholesterol, esters of cholesterol, LDL lipoprotein, HDL lipoprotein, and oxidized LDL lipoprotein,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

11. A composition, consisting of:

(i) a polymeric carrier; and

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein each hydrophobic group of the plurality of hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a targeting molecule covalently linked to the protective side chain, wherein the targeting molecule is selected from the group consisting of monocyte chemotactic protein 1, N-formyl-methionyl-leucyl-phenylalanine, granulocyte macrophage colony-stimulating factor (GM-CSF), colony stimulating factor-1, granulocyte macrophage colony-stimulating factor (GM-CSF) receptors, granulocyte macrophage colony-stimulating factor (GM-CSF) antibodies, colony stimulating factor-1 receptors, colony stimulating factor-1 antibodies, platelet factor 4;

TGF-fl growth factor, VEGF growth factor, E-selectin, VCAM-1 adhesive cell-surface glycoprotein, VCAM1f1 adhesive cell-surface glycoprotein, 11C-deoxy-D-glucose, C1 component of vascular inflammatory response, C1q component of vascular inflammatory response, C1r component of vascular inflammatory response, C1s component of vascular inflammatory response, C2 component of vascular inflammatory response, C3 component of vascular inflammatory response, C3a component of vascular inflammatory response, C3b component of vascular inflammatory response, C4 component of vascular inflammatory response, C4C2 component of vascular inflammatory response, C4C2C3b component of vascular inflammatory response, C5a component of vascular inflammatory response, C5b component of vascular inflammatory response, C5a component of vascular inflammatory response, interleukin 1, interleukin 10, interleukin 2, interleukin 3, interleukin 6, interleukin 7, interleukin 8, interferon α

, interferon γ

, tumor necrosis factor TNF-α

, polyethylene glycol coated liposomes, cholesterol, esters of cholesterol, LDL lipoprotein, HDL lipoprotein, and oxidized LDL lipoprotein; and

(iv) a load molecule dissociably linked to the hydrophobic groups,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

12. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein each hydrophobic group of the plurality of hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a targeting molecule covalently linked to the protective side chain, wherein the targeting molecule is selected from the group consisting of monocyte chemotactic protein 1, N-formyl-methionyl-leucyl-phenylalanine, granulocyte macrophage colony-stimulating factor (GM-CSF), colony stimulating factor-1, granulocyte macrophage colony-stimulating factor (GM-CSF) receptors, granulocyte macrophage colony-stimulating factor (GM-CSF) antibodies, colony stimulating factor-1 receptors, colony stimulating factor-1 antibodies, platelet factor 4;

TGF-fl growth factor, VEGF growth factor, E-selectin, VCAM-1 adhesive cell-surface glycoprotein, VCAM1f1 adhesive cell-surface glycoprotein, 11C-deoxy-D-glucose, C1 component of vascular inflammatory response, C1q component of vascular inflammatory response, C1r component of vascular inflammatory response, C1s component of vascular inflammatory response, C2 component of vascular inflammatory response, C3 component of vascular inflammatory response, C3a component of vascular inflammatory response, C3b component of vascular inflammatory response, C4 component of vascular inflammatory response, C4C2 component of vascular inflammatory response, C4C2C3b component of vascular inflammatory response, C5a component of vascular inflammatory response, C5b component of vascular inflammatory response, C5a component of vascular inflammatory response, interleukin 1, interleukin 10, interleukin 2, interleukin 3, interleukin 6, interleukin 7, interleukin 8, interferon α

, interferon γ

, tumor necrosis factor TNF-α

, polyethylene glycol coated liposomes, cholesterol, esters of cholesterol, LDL lipoprotein, HDL lipoprotein, and oxidized LDL lipoprotein; and

(iv) an orienting molecule covalently linked to the carrier,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

13. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of hydrophobic groups with a covalently linked protective side chain, wherein each hydrophobic group has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a targeting molecule covalently linked to the protective side chain, wherein the targeting molecule is selected from the group consisting of monocyte chemotactic protein 1, N-formyl-methionyl-leucyl-phenylalanine, granulocyte macrophage colony-stimulating factor (GM-CSF), colony stimulating factor-1, granulocyte macrophage colony-stimulating factor (GM-CSF) receptors, granulocyte macrophage colony-stimulating factor (GM-CSF) antibodies, colony stimulating factor-1 receptors, colony stimulating factor-1 antibodies, platelet factor 4;

TGF-fl growth factor, VEGF growth factor, E-selectin, VCAM-1 adhesive cell-surface glycoprotein, VCAM1f1 adhesive cell-surface glycoprotein, 11C-deoxy-D-glucose, C1 component of vascular inflammatory response, C1q component of vascular inflammatory response, C1r component of vascular inflammatory response, C1s component of vascular inflammatory response, C2 component of vascular inflammatory response, C3 component of vascular inflammatory response, C3a component of vascular inflammatory response, C3b component of vascular inflammatory response, C4 component of vascular inflammatory response, C4C2 component of vascular inflammatory response, C4C2C3b component of vascular inflammatory response, C5a component of vascular inflammatory response, C5b component of vascular inflammatory response, C5a component of vascular inflammatory response, interleukin 1, interleukin 10, interleukin 2, interleukin 3, interleukin 6, interleukin 7, interleukin 8, interferon α

, interferon γ

, tumor necrosis factor TNF-α

, polyethylene glycol coated liposomes, cholesterol, esters of cholesterol, LDL lipoprotein, HDL lipoprotein, and oxidized LDL lipoprotein;

(iv) an orienting molecule covalently linked to the carrier, and

(v) a load molecule dissociably linked to the hydrophobic groups and/or the orienting molecule,

wherein each hydrophobic group of the plurality of hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and hydrophobic group weights;

wherein the weight ratio of the protective side chains to the hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

14. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain; and

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight,

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

15. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight, and

(iv) a load molecule dissociably linked to the first, the second, or both the first and the second hydrophobic groups;

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

16. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight; and

(iv) an orienting molecule covalently linked to the carrier,

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

17. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight;

(iv) an orienting molecule covalently linked to the carrier; and

(v) a load molecule dissociably linked to the first, the second, or both the first and the second hydrophobic groups and/or the orienting molecule,

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

18. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight; and

(iv) a targeting molecule covalently linked to the protective side chain,

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

19. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight;

(iv) a targeting molecule covalently linked to the protective side chain; and

(v) a load molecule dissociably linked to the first, the second, or both the first and the second hydrophobic groups,

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

20. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight;

(iv) a targeting molecule covalently linked to the protective side chain;

(v) a load molecule dissociably linked to the first, the second, or both the first and the second hydrophobic groups; and

(vi) an orienting molecule covalently linked to the carrier,

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

21. A composition, consisting of:

(i) a polymeric carrier;

(ii) a plurality of first hydrophobic groups with a covalently linked protective side chain, wherein each first hydrophobic group of the plurality of first hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the protective side chain;

(iii) a plurality of second hydrophobic groups, wherein each second hydrophobic group of the plurality of second hydrophobic groups is covalently linked to the carrier and has a molecular weight less than 1,000 Daltons independent of the carrier weight;

(iv) a targeting molecule covalently linked to the protective side chain;

(v) an orienting molecule covalently linked to the carrier; and

(vi) a load molecule dissociably linked to the first, the second, or both the first and the second hydrophobic groups and/or the orienting molecule,

wherein each first hydrophobic group of the plurality of first hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight between 150 to 1000 Daltons independent of the carrier and protective side chain weights;

wherein the protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof;

wherein the protective side chain has a molecular weight between about 400 and 20,000 Daltons independent of the carrier and first and second hydrophobic group weights;

wherein the weight ratio of the protective side chains to the first hydrophobic groups is more than 17;

1; and

wherein the composition is soluble in an aqueous solvent.

22. A composition consisting of

(i) a carrier;

(ii) a plurality of first hydrophobic groups, wherein each first hydrophobic group of the plurality of first hydrophobic groups is covalently linked to the carrier, is capable of binding a load molecule, comprises an alkyl group of 8-36 carbons, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein, each first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight, wherein the ratio of the first protective side chains to the hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer; and

(iv) a plurality of second protective side chains and a plurality of second hydrophobic groups capable of binding a load molecule, wherein each second protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each second hydrophobic group of the plurality of second hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the second protective side chain;

wherein each second hydrophobic group of the plurality of second hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight of less than 1,000 Daltons independent of the carrier and protective side chain weights; and

wherein the second protective side chain covalently linked to the second hydrophobic group has a molecular weight between 400 and 20,000 Daltons independent of the second hydrophobic group weight.

23. A composition consisting of

(i) a carrier;

(ii) a plurality of first hydrophobic groups, wherein the first hydrophobic group is covalently linked to the carrier, is capable of binding a load molecule, comprises an alkyl group of 8-36 carbons, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein, each first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight,

wherein the ratio of the first protective side chains to the first hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer;

(iv) a plurality of second protective side chains and a plurality of second hydrophobic groups capable of binding a load molecule, wherein each second protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each second hydrophobic group of the plurality of second hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the second protective side chain;

wherein each second hydrophobic group of the plurality of second hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight of less than 1,000 Daltons independent of the carrier and protective side chain weights; and

wherein the second protective side chain covalently linked to the second hydrophobic group has a molecular weight between 400 and 20,000 Daltons independent of the second hydrophobic group weight; and

(v) a load molecule dissociably linked to the first, the second, or both the first and the second hydrophobic groups, wherein the load molecule is a therapeutic agent.

24. The composition of claim 23, wherein the therapeutic agent is selected from the group consisting of glucagon-like-peptide, exenatide, Gastric inhibitory polypeptide (GIP), Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, interferon, interleukin, tumor necrosis factor, auristatin, insulin, insulin-like growth factor, growth hormone, nerve growth factor, brain-derived neurotrophic factor, endostatin, angiostatin, thrombospondin, blood clotting factor VII, blood clotting factor VIII, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), thrombopoietin, calcitonin, parathyroid hormone (PTH), erythropoietin, atrial natriuretic factor, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, vasopressin, terlipressin, desmopressin, vasoactive intestinal peptide (VIP), anti-bacterial agents, anti-fungal agents, anti-viral agents, doxorubicin, and vitamins.

25. The composition of claim 23 wherein the therapeutic agent is glucagon-like-peptide, Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, or atrial natriuretic factor.

34. A method of treating diabetes in mammals, comprising administering a therapeutically effective amount of a composition of claim 25, wherein the therapeutic agent is selected from the group consisting of glucagon-like-peptide, Epidermal Growth Factor (EGF) receptor ligand, and Gastrin.

26. A composition consisting of

(i) a carrier;

(ii) a plurality of first hydrophobic groups, wherein each first hydrophobic group of the plurality of first hydrophobic groups is covalently linked to the carrier, is capable of binding a load molecule, comprises an alkyl group of 8-36 carbons, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein, each first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight, wherein the ratio of the first protective side chains to the first hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer;

(iv) a plurality of second protective side chains and a plurality of second hydrophobic groups capable of binding a load molecule, wherein each second protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each second hydrophobic group of the plurality of second hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the second protective side chain;

wherein each second hydrophobic group of the plurality of second hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight of less than 1,000 Daltons independent of the carrier and protective side chain weights; and

wherein the second protective side chain covalently linked to the second hydrophobic group has a molecular weight between 400 and 20,000 Daltons independent of the second hydrophobic group weight; and

(v) an orienting molecule covalently linked to the carrier, wherein the orienting molecule is selected from the group consisting of sulfate, sulfonate, phosphate, phosphonate, bisphosphonate, lysine, and arginine.

27. A composition consisting of

(i) a carrier;

(ii) a plurality of first hydrophobic groups, wherein each first hydrophobic group of the plurality of first hydrophobic groups is covalently linked to the carrier, is capable of binding a load molecule, comprises an alkyl group of 8-36 carbons, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein, each first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight, wherein the ratio of the first protective side chains to the first hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer;

(iv) a plurality of second protective side chains and a plurality of second hydrophobic groups capable of binding a load molecule, wherein each second protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each second hydrophobic group of the plurality of second hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the second protective side chain;

wherein each second hydrophobic group of the plurality of second hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight of less than 1,000 Daltons independent of the carrier and protective side chain weights; and

wherein the second protective side chain covalently linked to the second hydrophobic group has a molecular weight between 400 and 20,000 Daltons independent of the second hydrophobic group weight;

(v) an orienting molecule covalently linked to the carrier, wherein the orienting molecule is selected from the group consisting of sulfate, sulfonate, phosphate, phosphonate, bisphosphonate, lysine, and arginine; and

(vi) a load molecule dissociably linked to the first, the second, or both the first and the second hydrophobic groups and/or the orienting molecule.

28. A composition consisting of

(i) a carrier;

(ii) a plurality of first hydrophobic groups, wherein each first hydrophobic group of the plurality of first hydrophobic groups is covalently linked to the carrier, is capable of binding a load molecule, comprises an alkyl group of 8-36 carbons, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein each first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight, wherein the ratio of the first protective side chains to the first hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer;

(iv) a plurality of second protective side chains and a plurality of second hydrophobic groups capable of binding a load molecule, wherein each second protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each second hydrophobic group of the plurality of second hydrophobic groups has a first end that is covalently linked to the carrier and a second end that is covalently linked to the second protective side chain;

wherein each second hydrophobic group of the plurality of second hydrophobic groups comprises an alkyl group of 8-36 carbons and has a molecular weight of less than 1,000 Daltons independent of the carrier and protective side chain weights; and

wherein the second protective side chain covalently linked to the second hydrophobic group has a molecular weight between 400 and 20,000 Daltons independent of the second hydrophobic group weight, and

(v) a targeting molecule covalently linked to the first, second, or both the first and second protective side chains, wherein the targeting molecule is selected from the group consisting of monocyte chemotactic protein 1, N-formyl-methionyl-leucyl-phenylalanine, granulocyte macrophage colony-stimulating factor (GM-CSF), colony stimulating factor-1, granulocyte macrophage colony-stimulating factor (GM-CSF) receptors, granulocyte macrophage colony-stimulating factor (GM-CSF) antibodies, colony stimulating factor-1 receptors, colony stimulating factor-1 antibodies, platelet factor 4;

TGF-fl growth factor, VEGF growth factor, E-selectin, VCAM-1 adhesive cell-surface glycoprotein, VCAM1f1 adhesive cell-surface glycoprotein, 11C-deoxy-D-glucose, C1 component of vascular inflammatory response, C1q component of vascular inflammatory response, C1r component of vascular inflammatory response, C1s component of vascular inflammatory response, C2 component of vascular inflammatory response, C3 component of vascular inflammatory response, C3a component of vascular inflammatory response, C3b component of vascular inflammatory response, C4 component of vascular inflammatory response, C4C2 component of vascular inflammatory response, C4C2C3b component of vascular inflammatory response, C5a component of vascular inflammatory response, C5b component of vascular inflammatory response, C5a component of vascular inflammatory response, interleukin 1, interleukin 10, interleukin 2, interleukin 3, interleukin 6, interleukin 7, interleukin 8, interferon α

, interferon γ

, tumor necrosis factor TNF-α

, polyethylene glycol coated liposomes, cholesterol, esters of cholesterol, LDL lipoprotein, HDL lipoprotein, and oxidized LDL lipoprotein.

29. A composition consisting of

(i) a carrier;

(ii) a plurality of hydrophobic groups, wherein each hydrophobic group of the plurality of hydrophobic groups is covalently linked to the carrier, is capable of binding a load molecule, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein, each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight, wherein the ratio of the protective side chains to the hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer,

wherein the first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

(iv) a load molecule dissociably linked to the hydrophobic groups, wherein the load molecule is a therapeutic agent selected from the group consisting of glucagon-like-peptide, exenatide, Gastric inhibitory polypeptide (GIP), Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, interferon, interleukin, tumor necrosis factor, insulin, insulin-like growth factor, growth hormone, nerve growth factor, brain-derived neurotrophic factor, endostatin, angiostatin, thrombospondin, blood clotting factor VII, blood clotting factor VIII, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), thrombopoietin, calcitonin, parathyroid hormone (PTH) atrial natriuretic factor, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, vasopressin, terlipressin, desmopressin, vasoactive intestinal peptide (VIP), anti-bacterial agents, anti-fungal agents, anti-viral agents, doxorubicin, auristatin, and vitamins.

30. The composition of claim 29 wherein the therapeutic agent is glucagon-like-peptide, Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, or atrial natriuretic factor.

31. A composition consisting of

(i) a carrier;

(ii) a plurality of hydrophobic groups, wherein each hydrophobic group of the plurality of hydrophobic groups is covalently linked to the carrier, is capable of binding a load molecule, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein, each first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight, wherein the ratio of the protective side chains to the hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer;

(iv) a load molecule dissociably linked to the hydrophobic groups, wherein the load molecule is a therapeutic agent selected from the group consisting of glucagon-like-peptide, exenatide, Gastric inhibitory polypeptide (GIP), Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, interferon, interleukin, tumor necrosis factor, insulin, insulin-like growth factor, growth hormone, nerve growth factor, brain-derived neurotrophic factor, endostatin, angiostatin, thrombospondin, blood clotting factor VII, blood clotting factor VIII, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), thrombopoietin, calcitonin, parathyroid hormone (PTH), erythropoietin, atrial natriuretic factor, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, vasopressin, terlipressin, desmopressin, vasoactive intestinal peptide (VIP), anti-bacterial agents, anti-fungal agents, anti-viral agents, doxorubicin, auristatin, and vitamins; and

(v) an orienting molecule covalently linked to the carrier, wherein the orienting molecule is selected from the group consisting of sulfate, sulfonate, phosphate, phosphonate, bisphosphonate, lysine, and arginine.

32. The composition of claim 31, wherein the load molecule is further dissociably linked to the orienting molecule.

33. A composition comprising

(i) a carrier;

(ii) a plurality of first hydrophobic groups, wherein each hydrophobic group of the plurality of hydrophobic groups is covalently linked to the carrier, is capable of binding a load molecule, and has a molecular weight of less than about 1,000 Daltons independent of the carrier weight;

(iii) a plurality of first protective side chains, wherein, each first protective side chain is polyethylene glycol, polypropylene glycol, a co-polymer of polyethylene glycol and polypropylene glycol, or an alkoxy derivative thereof; and

each first protective side chain is covalently linked to the carrier and has a molecular weight between about 400 and 20,000 Daltons independent of the carrier weight, wherein the ratio of the first protective side chains to the hydrophobic groups is more than 17;

1, whereby the composition is soluble in aqueous buffer;

(iv) a load molecule dissociably linked to the hydrophobic groups, wherein the load molecule is a therapeutic agent selected from the group consisting of glucagon-like-peptide, exenatide, Gastric inhibitory polypeptide (GIP), Epidermal Growth Factor (EGF) receptor ligand, Transforming Growth Factor alpha (TGF-alpha), Betacellulin, Gastrin/Cholecystokinin receptor ligand, interferon, interleukin, tumor necrosis factor, insulin, insulin-like growth factor, growth hormone, nerve growth factor, brain-derived neurotrophic factor, endostatin, angiostatin, thrombospondin, blood clotting factor VII, blood clotting factor VIII, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), thrombopoietin, calcitonin, parathyroid hormone (PTH), erythropoietin, atrial natriuretic factor, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, vasopressin, terlipressin, desmopressin, vasoactive intestinal peptide (VIP), anti-bacterial agents, anti-fungal agents, anti-viral agents, doxorubicin, auristatin, and vitamins, and

(v) a targeting molecule covalently linked to the first protective side chains, wherein the targeting molecule is selected from the group consisting of monocyte chemotactic protein 1, N-formyl-methionyl-leucyl-phenylalanine, granulocyte macrophage colony-stimulating factor (GM-CSF), colony stimulating factor-1, granulocyte macrophage colony-stimulating factor (GM-CSF) receptors, granulocyte macrophage colony-stimulating factor (GM-CSF) antibodies, colony stimulating factor-1 receptors, colony stimulating factor-1 antibodies, platelet factor 4;

TGF-fl growth factor, VEGF growth factor, E-selectin, VCAM-1 adhesive cell-surface glycoprotein, VCAM1f1 adhesive cell-surface glycoprotein, 11C-deoxy-D-glucose, C1 component of vascular inflammatory response, C1q component of vascular inflammatory response, C1r component of vascular inflammatory response, C1s component of vascular inflammatory response, C2 component of vascular inflammatory response, C3 component of vascular inflammatory response, C3a component of vascular inflammatory response, C3b component of vascular inflammatory response, C4 component of vascular inflammatory response, C4C2 component of vascular inflammatory response, C4C2C3b component of vascular inflammatory response, C5a component of vascular inflammatory response, C5b component of vascular inflammatory response, C5a component of vascular inflammatory response, interleukin 1, interleukin 10, interleukin 2, interleukin 3, interleukin 6, interleukin 7, interleukin 8, interferon α

, interferon γ

, tumor necrosis factor TNF-α

, polyethylene glycol coated liposomes, cholesterol, esters of cholesterol, LDL lipoprotein, HDL lipoprotein, and oxidized LDL lipoprotein, and lipid receptors.