Drug delivery means

Abstract

The invention broadly comprises a chemical composition including a plurality of cholesteryl esters arranged to form a vesicle. In several embodiments, all of the plurality of cholesteryl esters have a same molecular length, which in some embodiments provides a vesicle having a generally smooth outer surface, while in other embodiments, a portion of the plurality of cholesteryl esters have different molecular lengths, which in some embodiments provides a vesicle having a generally irregular outer surface. In yet further embodiments, a shape of the vesicle is selected from the group consisting of spherical, oval, disc-like, tubular and polyhedral shapes, and in yet other embodiments, a wall of the vesicle is selected from the group consisting of a monolayer and a bilayer. In still further embodiments, the chemical composition further includes a polyethylene glycol coat of mixed polymer size. In some embodiments, the plurality of cholesteryl esters include at least two different cholesteryl esters, and in some of these embodiments, the at least two different cholesteryl esters are selected from the group consisting of: cholesteryl myristate, cholesteryl laurate, cholesteryl dodeconate, cholesteryl palmitate, cholesteryl arachidonate, cholesteryl behenate, cholesteryl linoleate, cholesteryl linolenate, cholesteryl oleate and cholesteryl stearate.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

The nature and mode of operation of the present invention will now be more fully described in the following detailed description of the invention taken with the accompanying drawing figures, in which:

FIG. 1 is a diagram of a present invention cholestosome membrane;

FIG. 2 is an isopotential model of a present invention cholestosome;

FIG. 3 is an isopotential model of a present invention cholestosome;

FIG. 4 is an isopotential model of a present invention cholestosome;

FIG. 5 is an example of phospholipids;

FIG. 6A is a graph of the binary combination of Cholesterol with 25-OH;

FIG. 6B is an expanded graph view of Cholesterol and 25-OH;

FIG. 7A is a graph of the binary combination of Cholesterol with 7-Keto;

FIG. 7B is an expanded graph view of Cholesterol and 7-Keto;

FIG. 8A is a graph of the binary combinations of Cholesterol and Cholestane Triol;

FIG. 8B is an expanded graph view of Cholesterol and Cholestane Triol;

FIG. 9A is a graph of the binary combinations of Cholesterol and 20-Alpha;

FIG. 9B is an expanded graph view of Cholesterol and 20-Alpha;

FIG. 10A is a graph of the binary combinations of Cholesterol with 7-Beta;

FIG. 10B is an expanded graph view of Cholesterol and 7-Beta;

FIG. 11A is a graph of the binary combinations of 25-OH with 7-Keto;

FIG. 11B is an expanded graph view of 25-OH and 7-Keto;

FIG. 12A is a graph of the binary combinations of 25-OH with Cholestane Triol;

FIG. 12B is an expanded graph view of 25-OH and Cholestane Triol;

FIG. 13A is a graph of the binary combinations of 25-OH with 20-Alpha;

FIG. 13B is an expanded graph view of 25-OH and 20-Alpha;

FIG. 14A is a graph of the binary combinations of 25-OH with 7-Beta;

FIG. 14B is an expanded graph view of 25-OH and 7-Beta;

FIG. 15A is a graph of the binary combinations of Cholestane Triol with 7-Keto;

FIG. 15B is an expanded graph view of Cholestane Triol and 7-Keto

FIG. 16A is a graph of the binary combinations of Cholestane Triol with 20-Alpha;

FIG. 16B is an expanded graph view of Cholestane Triol and 20-Alpha;

FIG. 17A is a graph of the binary combinations of Cholestane Triol with 7-Beta;

FIG. 17B is an expanded graph view of Cholestane Triol and 7-Beta;

FIG. 18A is a graph of the binary combinations of 7-Keto with 20-Alpha;

FIG. 18B is an expanded graph view of 7-Keto and 20-Alpha;

FIG. 19A is a graph of the binary combinations of 7-Keto with 7-Beta;

FIG. 19B is an expanded graph view of 7-Keto and 7-Beta;

FIG. 20A is a graph of the binary combinations of 20-Alpha with 7-Beta;

FIG. 20B is an expanded graph view of 20-Alpha and 7-Beta;

FIG. 21A is, a phase diagram for Cholesteryl Oleate and Cholesteryl Linoleate;

FIG. 21B is an expanded phase diagram of Cholesteryl Oleate and Cholesteryl Linoleate;

FIG. 22A is a phase diagram of Cholesteryl Oleate and Cholesteryl Linolenate;

FIG. 22B is an expanded phase diagram of Cholesteryl Oleate and Cholesteryl Linolenate;

FIG. 23A is a phase diagram of Cholesteryl Linoleate and Cholesteryl Linolenate;

FIG. 23B is an expanded phase diagram of Cholesteryl Linoleate and Cholesteryl Linolenate;

FIG. 24A is a phase diagram of Cholesteryl Laurate and Cholesteryl Myristate;

FIG. 24B is an expanded phase diagram of Cholesteryl Laurate and Cholesteryl Myristate;

FIG. 25A is a phase diagram of Cholesteryl Laurate and Cholesteryl Palmitate;

FIG. 25B is an expanded phase diagram of Cholesteryl Laurate and Cholesteryl Palmitate;

FIG. 26A is a phase diagram of Cholesteryl Laurate and Cholesteryl Stearate;

FIG. 26B is an expanded phase diagram of Cholesteryl Laurate and Cholesteryl Stearate;

FIG. 27A is a phase diagram of Cholesteryl Laurate and Cholesteryl Behenate;

FIG. 27B is an expanded phase diagram of Cholesteryl Laurate and Cholesteryl Behenate;

FIG. 28A is a phase diagram of Cholesteryl Myristate and Cholesteryl Palmitate;

FIG. 28B is an expanded phase diagram of Cholesteryl Myristate and Cholesteryl Palmitate;

FIG. 29A is a phase diagram of Cholesteryl Myristate and Cholesteryl Stearate;

FIG. 29B is an expanded phase diagram of Cholesteryl Myristate and Cholesteryl Stearate;

FIG. 30A is a phase diagram of Cholesteryl Myristate and Cholesteryl Behenate;

FIG. 30B is an expanded phase diagram of Cholesteryl Myristate and Cholesteryl Behenate;

FIG. 31A is a phase diagram of Cholesteryl Palmitate and Cholesteryl Stearate;

FIG. 31B is an expanded phase diagram of Cholesteryl Palmitate and Cholesteryl Stearate;

FIG. 32A is a phase diagram of Cholesteryl Palmitate and Cholesteryl Behenate;

FIG. 32B is an expanded phase diagram of Cholesteryl Palmitate and Cholesteryl Behenate;

FIG. 33A is a phase diagram of Cholesteryl Stearate and Cholesteryl Behenate;

FIG. 33B is an expanded phase diagram of Cholesteryl Stearate and Cholesteryl Behenate;

FIG. 34 is a dot surface model of Cholesterol;

FIG. 35 is a dot surface model of 7-Ketocholesterol;

FIG. 36 is a dot surface model of 25-Hydroxycholesterol;

FIG. 37 is a dot surface model of Cholestane Triol;

FIG. 38 is a dot surface model of 7B-Hydroxycholesterol;

FIG. 39 is a dot surface model of 20A-Hydroxycholesterol;

FIG. 40 shows line structures for Cholesterol and Selected Oxidized Derivatives;

FIG. 41 shows the packing of Cholesterol and 25-Hydroxycholesterol;

FIG. 42 shows the packing of Cholesterol and 7-Ketocholesterol;

FIG. 43A shows the packing of Cholesterol and Cholestane Triol;

FIG. 43B shows an alternative packing of Cholesterol and Cholestane Triol;

FIG. 44 shows the packing of Cholesterol and 20A-Hydroxycholesterol;

FIG. 45 shows the packing of Cholesterol and 7B-Hydroxycholesterol;

FIG. 46 shows the packing of 25-Hydroxycholesterol and 7-Ketocholesterol;

FIG. 47 shows the packing of 25-Hydroxycholesterol and Cholestane Triol;

FIG. 48 shows the packing of 25-Hydroxycholesterol and 20A-Hydroxycholesterol;

FIG. 49 shows the packing of 25-Hydroxycholesterol and 7B-Hydroxycholesterol;

FIG. 50 shows the packing of Cholestane Triol and 7-Ketocholesterol;

FIG. 51 shows the packing of Cholestane Triol and 20A-Hydroxycholesterol;

FIG. 52 shows the packing of Cholestane Triol and 7B-Hydroxycholesterol;

FIG. 53 shows the packing of 7-Ketocholesterol and 20A-Hydroxycholesterol;

FIG. 54 shows the packing of 7-Ketocholesterol and 7B-Hydroxycholesterol;

FIG. 55 shows the packing of 20A-Hydroxycholesterol and 7B-Hydroxycholesterol;

FIG. 56 is a dot surface model for Cholesteryl Arachidonate;

FIG. 57 is a dot surface model for Cholesteryl Behenate;

FIG. 58 is a dot surface model for Cholesteryl Dodecanoate (laurate);

FIG. 59 is a dot surface model for Cholesteryl Linoleate;

FIG. 60 is a dot surface model for Cholesteryl Linolenate;

FIG. 61 is a dot surface model for Cholesteryl Myristate;

FIG. 62 is a dot surface model for Cholesteryl Oleate;

FIG. 63 is a dot surface model for Cholesteryl Palmitate;

FIG. 64 is a dot surface model for Cholesteryl Stearate;

FIG. 65 shows line structures for Unsaturated Cholesteryl Esters Studied;

FIG. 66 shows line structures for Saturated Cholesteryl Esters Studied;

FIG. 67 shows the packing of Cholesteryl Oleate and Cholesteryl Linoleate;

FIG. 68 shows the packing of Cholesteryl Oleate and Cholesteryl Linolenate;

FIG. 69 shows the packing of Cholesteryl Linoleate and Cholesteryl Linolenate;

FIG. 70 shows the packing of Cholesteryl Dodecanoate and Cholesteryl Myristate;

FIG. 71 shows the packing of Cholesteryl Dodecanoate and Cholesteryl Palmitate;

FIG. 72 shows the packing of Cholesteryl Dodecanoate and Cholesteryl Stearate;

FIG. 73 shows the packing of Cholesteryl Dodecanoate and Cholesteryl Behenate;

FIG. 74 shows the packing of Cholesteryl Myristate and Cholesteryl Palmitate;

FIG. 75 shows the packing of Cholesteryl Myristate and Cholesteryl Stearate;

FIG. 76 shows the packing of Cholesteryl Myristate and Cholesteryl Behenate;

FIG. 77 shows the packing of Cholesteryl Palmitate and Cholesteryl Stearate;

FIG. 78 shows the packing of Cholesteryl Palmitate and Cholesteryl Behenate;

FIG. 79 shows the packing Cholesteryl Stearate and Cholesteryl Behenate; and,

FIG. 80 shows photomicrographs of cells showing presence of a fluorescent indicator, photomicrographs of cells showing staining of the nuclei and photomicrographs of cells.

Claims

1. A chemical composition comprising: a plurality of cholesteryl esters arranged to form a vesicle.

2. The chemical composition of claim 1 wherein all of said plurality of cholesteryl esters have a same molecular length.

3. The chemical composition of claim 2 wherein said vesicle has a generally smooth outer surface.

4. The chemical composition of claim 1 wherein a portion of said plurality of cholesteryl esters have different molecular lengths.

5. The chemical composition of claim 4 wherein said vesicle has a generally irregular outer surface.

6. The chemical composition of claim 1 wherein a shape of said vesicle is selected from the group consisting of spherical, oval, disc-like, tubular and polyhedral shapes.

7. The chemical composition of claim 1 wherein a wall of said vesicle is selected from the group consisting of a monolayer and a bilayer.

8. The chemical composition of claim 1 further comprising a polyethylene glycol coat of mixed polymer size.

9. The chemical composition of claim 1 wherein said plurality of cholesteryl esters comprise at least two different cholesteryl esters.

10. The chemical composition of claim 9 wherein said at least two different cholesteryl esters are selected from the group consisting of: cholesteryl myristate, cholesteryl laurate, cholesteryl dodeconate, cholesteryl palmitate, cholesteryl arachidonate, cholesteryl behenate, cholesteryl linoleate, cholesteryl linolenate, cholesteryl oleate and cholesteryl stearate.

11. The chemical composition of claim 1 where said composition is clear dispersed in both hydrophilic and hydrophobic systems.

12. The chemical composition of claim 11 where said composition is smaller than wavelengths of visible light.

13. A method of delivering a drug to a cell comprising the steps of: a) combining a pharmaceutically effective amount of at least one drug with at least one cholestosome; and,b) utilizing said at least one cholestosome to introduce said drug to the cell.

14. The method of delivering a drug according to claim 13 further comprising the step of: c) depositing said at least one drug within said cell.

15. A method of manufacturing at least one cholestosome comprising the steps of: a) mixing at least one cholesteryl ester in a first solvent to form a composition;b) mixing said composition of step a) with a second solvent until said at least one cholesteryl ester, said first solvent and said second solvent form a homogenous dispersion; and,c) evaporating said first solvent leaving said at least one cholestosome in said second solvent.

16. A method of manufacturing a drug delivery system comprising the steps of: a) mixing at least one cholesteryl ester in a first solvent to form a composition;b) mixing said composition of step a) and at least one drug in a pharmaceutically effective amount in a second solvent until said at least one cholesteryl ester, said first solvent, said at least one drug and said second solvent form a homogenous dispersion; and,c) evaporating said first solvent leaving at least one cholestosome in said second solvent, wherein said at least one drug is combined with said at least one cholestosome.

17. The method of claim 16 where the drug is contained within the cholestosome.

18. The method of manufacturing a drug delivery system according to claim 16 wherein said first solvent is a non-polar solvent and said second solvent is a polar solvent.

19. A drug delivery system manufactured by the steps comprising: a) mixing at least one cholesteryl ester in a first solvent to form a composition;b) mixing said composition of step a) and at least one drug in a pharmaceutically effective amount in a second solvent until said at least one cholesteryl ester, said first solvent, said at least one drug and said second solvent form a homogenous dispersion; and,c) evaporating said first solvent leaving at least one cholestosome in said second solvent, wherein said at least one drug is combined with said at least one cholestosome.

20. The method of claim 19 wherein the drug is contained within the cholestosome.