Liposomal formulations of anthracycline agents and cytidine analogs
View Patent ↗Compositions which comprise an anthracycline agent, and a cytidine analog are encapsulated in liposomal carriers. The preferred anthracycline agent is selected from the group of daunorubicin, doxorubicin, and idarubicin, while the preferred cytidine analog is selected from the group of cytarabine, gemcitabine, or 5-azacytidine. The combination of the anthracycline agent and cytidine analog encapsulated in said liposomal carriers are useful in achieving a drug retention and a sustained drug release for each therapeutic agent.
1. A composition for parenteral administration to a subject which composition comprises liposomes having associated therewith daunorubicin and cytarabine in a mole ratio of daunorubicin:cytarabine of about 1:5 wherein the daunorubicin and cytarabine are associated with the liposomes so that said mole ratio is maintained in the blood for at least one hour after administration to the subject.
2. The composition of claim 1 , wherein the daunorubicin and cytarabine are co-encapsulated.
3. The composition of claim 1 , wherein the liposomes have a mean diameter of between 4.5 and 500 nm.
4. The composition of claim 3 , wherein the liposomes have a mean diameter of less than 250 nm.
5. The composition of claim 1 , wherein the liposomes comprise a phosphatidylcholine-containing lipid, and/or a charged lipid and/or a sterol.
6. The composition of claim 5 , wherein the liposomes comprise DSPC, DSPG and cholesterol in a mole ratio of about 7:2:1.
7. A method to treat a leukemia in a subject which comprises administering to said subject an effective amount of the composition of claim 1 .
8. The method of claim 7 , wherein the subject is a human.
9. The method of claim 7 , wherein the subject is a non-human mammal or avian.
10. The method of claim 8 , wherein the leukemia is ALL or AML.
11. The composition of claim 1 , wherein the composition comprises no therapeutic agents additional to the daunorubicin and cytarabine.
12. The composition of claim 1 , wherein the daunorubicin and cytarabine are co-encapsulated and said mole ratio is maintained in the blood for at least four hours after administration to the subject.
13. A composition for parental administration to a subject which composition comprises liposomes having associated therewith daunorubicin and cytarabine, wherein the daunorubicin:cytarabine mole ratio is about 1:5 and wherein
(a) the daunorubicin and cytarabine are co-encapsulated;
(b) said mole ratio is maintained in the blood for at least four hours after administration to the subject;
(c) the liposomes have a mean diameter of less than 250 nm; and
(d) the composition comprises no therapeutic agents in addition to the daunorubicin and cytarabine.
14. The composition of claim 13 , wherein the liposomes comprise DSPC, DSPG and cholesterol in a mole ratio of about 7:2:1.