1. A composition comprising a conjugate comprising cholesterol and adriamycin, wherein the conjugate has the following structure:
and a pharmaceutically acceptable carrier.
2. A composition comprising a conjugate comprising cholesterol and tetracycline wherein the conjugate has the folloeing structure:
and a pharmaceutically acceptable carrier.
3. The composition of claim 1, wherein the conjugate is contained within the core of low-density lipoprotein (LDL) particle comprising an artificial LDL comprising an outer phospholipid monolayer and a solid lipid core, wherein the outer phospholipid monolayer comprises at least one apolipoprotein.
4. The composition of claim 2, wherein the conjugate is contained within the core of low-density lipoprotein (LDL) particle comprising artificial LDL, an outer phospholipid monolayer and a solid lipid core, wherein the outer phospholipid monolayer comprises at least one apolipoprotein.
5. A conjugate comprising cholesterol and adriamycin or tetracycline, wherein the cholesterol and adriamycin or tetracycline are linked though an ester of a cyclic anhydride.
6. The conjugate of claim 5, wherein the cyclic anhydride is phthalate.
7. The conjugate of claim 5, wherein the cyclic anhydride is succinate.
8. A composition comprising the conjugate of claim 5 and a pharmaceutically acceptable carrier.
9. A conjugate comprising thiocholesterol and adriamycin or tetracycline, wherein the thiocholesterol and adriamycin or tetracycline are linked though a bifunctional crosslinking agent comprising a thioether linkage between the cholesterol and the crosslinking agent.
10. The conjugate of claim 9, wherein the bifunctional crosslinking agent is N-(p-Maleimidophenyl)isocynate (PMPI).
11. A composition comprising the conjugate of claim 9 and a pharmaceutically acceptable carrier.
12. A method for delivery adriamycin across the blood-brain barrier, said method comprising administering an effective amount of the composition of claim 3 to a mammal in need thereof.
13. A method for delivery tetracycline across the blood-brain barrier, said method comprising administering an effective amount of the composition of claim 4 to a mammal in need thereof.
14. A method of producing a low-density lipoprotein (LDL) particle comprising the steps of: 1) suspending a mixture of phospholipids and lipids containing the conjugate of claim 1 in a buffer solution; 2) sonicating the solution to form the outer phospholipid monolayer and solid lipid core; and 3) adding a solution comprising at least one apolipoprotein, wherein the phospholipids and lipids are added in a ratio of about 12:1 by weight, and wherein the apolipoprotein is incorporated into the outer phospholipid monolayer.
15. The method of claim 14, wherein the artificial LDL particles produced have a diameter between 10 and 50 nm.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A thermoformed article stack segmenting apparatus, comprising:
a frame;
a stacked article guide channel carried by the frame and configured to receive and guide a stack of inter-nested articles exiting a female die of a thermoforming trim press;
a forward engaging drive finger;
a reciprocating actuator coupled with the finger to drive the finger forward in engagement with one separated stack of articles and to drive the finger rearward in a retractable state to separate another, successive stack of articles; and
a rearward engaging holding finger supported by the frame and configured to hold the another, successive stack while driving the forward engaging drive finger forward.
2. The thermoformed article stack segmenting apparatus of claim 1, wherein an array of juxtaposed stacked article guide channels are carried by the frame each configured to received a respective stack of inter-nested articles exiting females dies of a thermoforming trim press.