Ceramide anionic liposome compositions
AssigneeThe Penn State Research Foundation
InventorsMark Kester, Sriram S. Shanmugavelandy, Todd Fox
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Abstract
Described herein are pharmaceutical compositions according to aspects of the present invention which include one or more hydrophilic antineoplastic chemotherapeutics, such as vinca alkyloid antineoplastic chemotherapeutics, encapsulated in ceramide anionic liposomes. Methods of treatment of a subject having cancer using the pharmaceutical compositions are described, along with methods of making ceramide anionic liposomes which encapsulate one or more hydrophilic antineoplastic chemotherapeutics in the aqueous interior of the ceramide anionic liposomes.
Claims17
A pharmaceutical composition, comprising:
- a antineoplastic chemotherapeutic encapsulated in ceramide anionic liposomes.
A method of producing a pharmaceutical composition, comprising:
- providing a lipid mixture comprising at least one pegylated neutral lipid, wherein the total amount of pegylated neutral lipid is an amount in the range of 5-20 Molar percent, inclusive, and wherein at least half of the amount of included pegylated neutral lipid is N-Octanoyl-Sphingosine-1-succinyl(methoxy(polyethylene)glycol)750 (PEG(750) C8);
- at least one anionic lipid, wherein the total amount of anionic lipid is an amount in the range of 5-15 Molar percent, inclusive;
- one or more ceramides selected from C4 ceramide, C6 ceramide, C8 ceramide, C10 ceramide, C12 ceramide, C14 ceramide, C16 ceramide and C18 ceramide, in an amount in the range of 1-40 Molar percent, inclusive;
- and cationic or neutral lipids, with the proviso that the resulting lipid mixture has a net negative charge at physiological pH;
- sonicating the lipid mixture in the presence of an amount of a antineoplastic chemotherapeutic at a temperature in the range of 55-75 degrees Celsius, inclusive, to produce a sonicated mixture;
- and
- passing the sonicated mixture through a filter having pores of a desired size to produce liposomes having the desired size, at a temperature in the range of 67-75 degrees Celsius, producing a population of ceramide anionic liposomes, wherein the population comprises greater than 10% of the amount of the antineoplastic chemotherapeutic.
Dependencies are inferred from the claim text.