CA2564120A1 - Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes - Google Patents
Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes Download PDFInfo
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- CA2564120A1 CA2564120A1 CA002564120A CA2564120A CA2564120A1 CA 2564120 A1 CA2564120 A1 CA 2564120A1 CA 002564120 A CA002564120 A CA 002564120A CA 2564120 A CA2564120 A CA 2564120A CA 2564120 A1 CA2564120 A1 CA 2564120A1
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- release rate
- neutral lipid
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- active compound
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- 150000002632 lipids Chemical class 0.000 title claims abstract 83
- 230000007935 neutral effect Effects 0.000 title claims abstract 69
- 238000001727 in vivo Methods 0.000 title claims abstract 11
- 238000000034 method Methods 0.000 title claims 27
- 239000002502 liposome Substances 0.000 title claims 15
- 150000001875 compounds Chemical class 0.000 claims abstract 18
- 239000000203 mixture Substances 0.000 claims abstract 15
- 238000009472 formulation Methods 0.000 claims abstract 5
- 229940093609 tricaprylin Drugs 0.000 claims 11
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 claims 11
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 claims 8
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 claims 8
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 claims 8
- 229940117972 triolein Drugs 0.000 claims 8
- SKGWNZXOCSYJQL-BUTYCLJRSA-N 1,2,3-tripalmitoleoylglycerol Chemical compound CCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCC)COC(=O)CCCCCCC\C=C/CCCCCC SKGWNZXOCSYJQL-BUTYCLJRSA-N 0.000 claims 7
- SKGWNZXOCSYJQL-UHFFFAOYSA-N tripalmitoleoyl-sn-glycerol Natural products CCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCC)COC(=O)CCCCCCCC=CCCCCCC SKGWNZXOCSYJQL-UHFFFAOYSA-N 0.000 claims 7
- 239000000839 emulsion Substances 0.000 claims 6
- 238000002844 melting Methods 0.000 claims 6
- 230000008018 melting Effects 0.000 claims 6
- 239000003960 organic solvent Substances 0.000 claims 6
- 239000002904 solvent Substances 0.000 claims 6
- MAYCICSNZYXLHB-UHFFFAOYSA-N tricaproin Chemical compound CCCCCC(=O)OCC(OC(=O)CCCCC)COC(=O)CCCCC MAYCICSNZYXLHB-UHFFFAOYSA-N 0.000 claims 5
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N trilaurin Chemical compound CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 claims 4
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 claims 3
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 claims 3
- 229940093633 tricaprin Drugs 0.000 claims 3
- -1 trimyristolein Chemical compound 0.000 claims 3
- SDEURMLKLAEUAY-JFSPZUDSSA-N (2-{[(2r)-2,3-bis[(13z)-docos-13-enoyloxy]propyl phosphonato]oxy}ethyl)trimethylazanium Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCC\C=C/CCCCCCCC SDEURMLKLAEUAY-JFSPZUDSSA-N 0.000 claims 2
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 2
- HRTBOPUWPUXROO-VCZQVZGSSA-N (2-{[(2r)-2,3-bis(docosanoyloxy)propyl phosphonato]oxy}ethyl)trimethylazanium Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCCCCCC HRTBOPUWPUXROO-VCZQVZGSSA-N 0.000 claims 1
- YKIOPDIXYAUOFN-YACUFSJGSA-N (2-{[(2r)-2,3-bis(icosanoyloxy)propyl phosphonato]oxy}ethyl)trimethylazanium Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCCCC YKIOPDIXYAUOFN-YACUFSJGSA-N 0.000 claims 1
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 claims 1
- AEUCYCQYAUFAKH-DITNKEBASA-N 1,2-di-[(11Z)-eicosenoyl]-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCC\C=C/CCCCCCCC AEUCYCQYAUFAKH-DITNKEBASA-N 0.000 claims 1
- 229940083937 1,2-diarachidoyl-sn-glycero-3-phosphocholine Drugs 0.000 claims 1
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims 1
- BIABMEZBCHDPBV-BEBVUIBBSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-BEBVUIBBSA-N 0.000 claims 1
- IJFVSSZAOYLHEE-SSEXGKCCSA-N 1,2-dilauroyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCC IJFVSSZAOYLHEE-SSEXGKCCSA-N 0.000 claims 1
- DSNRWDQKZIEDDB-SQYFZQSCSA-N 1,2-dioleoyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC DSNRWDQKZIEDDB-SQYFZQSCSA-N 0.000 claims 1
- GPWHCUUIQMGELX-VHQDNGOZSA-N 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCC GPWHCUUIQMGELX-VHQDNGOZSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 150000001840 cholesterol esters Chemical class 0.000 claims 1
- 238000011534 incubation Methods 0.000 abstract 1
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- Medicinal Preparation (AREA)
Abstract
The rate of release of encapsulated active compound from a multivesicular liposomal (MVL) formulation is modified by selection of a neutral lipid component. A
family of MVL formulations containing different slow:fast release neutral lipid molar ratios displays different release rates depending upon the molar ratio of the fast release neutral lipid to the slow release neutral lipid in each member. Incubation in plasma or a plasma-like medium at in vivo temperatures so as to obtain a release rate curve for each allows selection from among the members of the family of a liposomal formulation with a desired rate of release in vivo.
family of MVL formulations containing different slow:fast release neutral lipid molar ratios displays different release rates depending upon the molar ratio of the fast release neutral lipid to the slow release neutral lipid in each member. Incubation in plasma or a plasma-like medium at in vivo temperatures so as to obtain a release rate curve for each allows selection from among the members of the family of a liposomal formulation with a desired rate of release in vivo.
Claims (23)
1. A method for modifying the rate of release of a biologically active compound encapsulated in a multivesicular liposome having a neutral lipid component comprising:
(i) forming an emulsion from a) a lipid component comprising a volatile organic solvent, an amphipathic lipid, and a neutral lipid component, said neutral lipid component having a melting point at or below an in vivo temperature at which the liposome is for use, said neutral lipid component comprising a molar ratio of from 1:0 to 0:1 of a slow release rate neutral lipid to a fast release rate neutral lipid, and b) an immiscible first aqueous component; wherein at least one biologically active compound is incorporated into either the lipid component or the first aqueous component, or both;
(ii) mixing the emulsion with an immiscible second aqueous component to form solvent spherules; and (iii)removing the volatile organic solvent from the solvent spherules to form multivesicular liposomes encapsulating the biologically active compound;
wherein the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid is selected to increase or decrease the rate of release of the biologically active compound, with an increase in the ratio corresponding to a decrease in release rate and wherein the slow release rate neutral lipid is selected from the group consisting of triolein, tripalmitolein, trimyristolein, trilaurin, tricaprin, and mixtures thereof, and the fast release rate neutral lipid is selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof.
(i) forming an emulsion from a) a lipid component comprising a volatile organic solvent, an amphipathic lipid, and a neutral lipid component, said neutral lipid component having a melting point at or below an in vivo temperature at which the liposome is for use, said neutral lipid component comprising a molar ratio of from 1:0 to 0:1 of a slow release rate neutral lipid to a fast release rate neutral lipid, and b) an immiscible first aqueous component; wherein at least one biologically active compound is incorporated into either the lipid component or the first aqueous component, or both;
(ii) mixing the emulsion with an immiscible second aqueous component to form solvent spherules; and (iii)removing the volatile organic solvent from the solvent spherules to form multivesicular liposomes encapsulating the biologically active compound;
wherein the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid is selected to increase or decrease the rate of release of the biologically active compound, with an increase in the ratio corresponding to a decrease in release rate and wherein the slow release rate neutral lipid is selected from the group consisting of triolein, tripalmitolein, trimyristolein, trilaurin, tricaprin, and mixtures thereof, and the fast release rate neutral lipid is selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof.
2. The method of claim 1, wherein the molar ratio of the neutral lipid component to all the lipids in the liposome is selected in the range from about 0.01 to about 0.21.
3. The method of claim 1, wherein the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid is selected in the range from about 1:1 to 1:100.
4. The method of claim 1, wherein the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid is selected in the range from about 1:4 to 1:27.
5. The method of claim 1, wherein the slow release rate neutral lipid is tripalmitolein.
6. The method of claim 1, wherein the slow release rate neutral lipid is triolein.
7. The method of claim 1, wherein the slow release rate neutral lipid is tricaprin.
8. The method of claim 6, wherein the fast release rate neutral lipid is tricaprylin or a mixture of tricaprylin and tricaproin.
9. A method for modifying the rate of release of a biologically active compound encapsulated in a multivesicular liposome, said method comprising utilizing a blend of slow release rate neutral lipids and fast release rate neutral lipids as a neutral lipid component in the multivesicular liposome in which the biologically active compound is encapsulated, said liposome having a molar ratio of from 1:0 to 0:1 of the slow release rate neutral lipids to the fast release rate neutral lipids;
wherein the rate of release of the biologically active compound increases in proportion with the molar ratio of the fast release rate neutral lipids to the slow release rate neutral lipids in the neutral lipid component, said neutral lipid component having a melting point at or below an in vivo temperature at which the liposome is for use; said fast release rate neutral lipid being selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof; and said slow release rate neutral lipids being selected from the group consisting of triolein, tripalmitolein and mixtures thereof.
wherein the rate of release of the biologically active compound increases in proportion with the molar ratio of the fast release rate neutral lipids to the slow release rate neutral lipids in the neutral lipid component, said neutral lipid component having a melting point at or below an in vivo temperature at which the liposome is for use; said fast release rate neutral lipid being selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof; and said slow release rate neutral lipids being selected from the group consisting of triolein, tripalmitolein and mixtures thereof.
10. The method of claim 9, wherein the biologically active compound is released in vivo, and the neutral lipid component has a melting point about or below an in vivo temperature.
11. The method of claim 9, wherein the biologically active compound is released at storage temperature, and the melting point of the neutral lipid component is about or below the storage temperature.
12. The method of claim 9, wherein when the fast release rate neutral lipid is tricaprylin, the molar ratio of triolein or tripalmitolein to tricaprylin is in the range from about 1:1 to 1:100.
13. The method of claim 9, wherein the molar ratio of the triolein or tripalmitolein to the fast release rate neutral lipid is in the range from about 1:1 to 1:27.
14. The method of claim 9, wherein the biologically active compound is released in vivo, and the fast release rate neutral lipid is tricaprylin.
15. A method for modifying the rate of release of a biologically active compound encapsulated in a multivesicular liposome having a neutral lipid component, said neutral lipid component having a melting point at or below an in vivo temperature at which the liposome is for use, said method comprising:
(i) forming an emulsion from a) a lipid component comprising a volatile organic solvent, an amphipathic lipid, and the neutral lipid component comprising a molar ratio of from 1:0 to 0:1 of a slow release rate neutral lipid to a fast release rate neutral lipid, and b) an immiscible first aqueous component; wherein at least one biologically active compound is incorporated into either the lipid component or the first aqueous component, or both;
(ii) mixing the emulsion with an immiscible second aqueous component to form solvent spherules; and (iii)removing the volatile organic solvent from the solvent spherules to form multivesicular liposomes encapsulating the biologically active compound;
wherein the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid is selected to increase or decrease the rate of release of the biologically active compound, with an increase in the ratio corresponding to a decrease in release rate and wherein the slow release rate neutral lipid is selected from the group consisting of propylene glycol diesters with eight and ten carbon acyl moieties, cholesterol esters, and mixtures thereof; and the fast release rate neutral lipid is selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof.
(i) forming an emulsion from a) a lipid component comprising a volatile organic solvent, an amphipathic lipid, and the neutral lipid component comprising a molar ratio of from 1:0 to 0:1 of a slow release rate neutral lipid to a fast release rate neutral lipid, and b) an immiscible first aqueous component; wherein at least one biologically active compound is incorporated into either the lipid component or the first aqueous component, or both;
(ii) mixing the emulsion with an immiscible second aqueous component to form solvent spherules; and (iii)removing the volatile organic solvent from the solvent spherules to form multivesicular liposomes encapsulating the biologically active compound;
wherein the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid is selected to increase or decrease the rate of release of the biologically active compound, with an increase in the ratio corresponding to a decrease in release rate and wherein the slow release rate neutral lipid is selected from the group consisting of propylene glycol diesters with eight and ten carbon acyl moieties, cholesterol esters, and mixtures thereof; and the fast release rate neutral lipid is selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof.
16. A method for selecting a multivesicular liposome formulation with a predetermined release rate of an encapsulated biologically active compound at a given temperature, said method comprising:
(i) preparing a family of multivesicular liposomal formulations wherein each member of the family is made by (1) forming an emulsion from (a) a lipid component comprising a volatile organic solvent, an amphipathic lipid, and a neutral lipid component, said neutral lipid component having a melting point at or below an in vivo temperature at which the liposome is for use, said neutral lipid component comprising a molar ratio of from 1:0 to 0:1 of a slow release rate neutral lipid to a fast release rate neutral lipid, and (b) an immiscible first aqueous component; wherein at least one biologically active compound is incorporated into either the lipid component or the first aqueous component, or both;
(2) mixing the emulsion with an immiscible second aqueous component to form solvent spherules;
and (3) removing the organic solvent from the solvent spherules to form multivesicular liposomes encapsulating the biologically active compound; wherein for each member of the family the neutral lipid component has a different molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid;
wherein the slow release rate neutral lipid is selected from the group consisting of triolein, tripalmitolein, trimyristolein, trilaurin, tricaprin, and mixtures thereof, and the fast release rate neutral lipid is selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof;
(ii) incubating each member of the family at a given temperature to obtain a family of release rate profiles; and (iii)selecting the family member with the neutral lipid component having the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid yielding the predetermined release rate profile.
(i) preparing a family of multivesicular liposomal formulations wherein each member of the family is made by (1) forming an emulsion from (a) a lipid component comprising a volatile organic solvent, an amphipathic lipid, and a neutral lipid component, said neutral lipid component having a melting point at or below an in vivo temperature at which the liposome is for use, said neutral lipid component comprising a molar ratio of from 1:0 to 0:1 of a slow release rate neutral lipid to a fast release rate neutral lipid, and (b) an immiscible first aqueous component; wherein at least one biologically active compound is incorporated into either the lipid component or the first aqueous component, or both;
(2) mixing the emulsion with an immiscible second aqueous component to form solvent spherules;
and (3) removing the organic solvent from the solvent spherules to form multivesicular liposomes encapsulating the biologically active compound; wherein for each member of the family the neutral lipid component has a different molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid;
wherein the slow release rate neutral lipid is selected from the group consisting of triolein, tripalmitolein, trimyristolein, trilaurin, tricaprin, and mixtures thereof, and the fast release rate neutral lipid is selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof;
(ii) incubating each member of the family at a given temperature to obtain a family of release rate profiles; and (iii)selecting the family member with the neutral lipid component having the molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid yielding the predetermined release rate profile.
17. The method of claim 16, wherein the amphipathic lipid is selected from the group of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and 1,2-dierucoyl-sn-glycero-3-phosphocholine (DEPC), and the slow release rate neutral lipid is triolein or tripalmitolein.
18. The method of claim 16, wherein the fast release rate neutral lipid is tricaprylin.
19. The method of claim 16, wherein the selected family member having the predetermined release rate has a molar ratio of the slow release rate neutral lipid to the fast release rate neutral lipid in the range from about 1:1 to about 1:54.
20. The method of claim 16, wherein the selected family member having the predetermined release rate has a molar ratio of the neutral lipid component to all the lipids in the lipid component in the range from about 0.01 to about 0.21.
21. The method of claim 16, wherein the release rate is in vivo and the slow release rate neutral lipid is triolein.
22. The method of claim 21, wherein the fast release rate neutral lipid is tricaprylin.
23. The method of claim 16, wherein the amphipathic lipid is selected from the group consisting of:
1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dilauroyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-diarachidoyl-sn-glycero-3-phosphocholine, 1,2-dibehenoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine, 1,2-dieicosenoyl-sn-glycero-3-phosphocholine, 1,2-dierucoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, and 1,2-dioleoyl-sn-glycero-3-phosphoglycerol.
1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dilauroyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-diarachidoyl-sn-glycero-3-phosphocholine, 1,2-dibehenoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine, 1,2-dieicosenoyl-sn-glycero-3-phosphocholine, 1,2-dierucoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, and 1,2-dioleoyl-sn-glycero-3-phosphoglycerol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2692302A CA2692302C (en) | 1997-01-31 | 1998-01-29 | Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/792,566 | 1997-01-31 | ||
| US08/792,566 US5891467A (en) | 1997-01-31 | 1997-01-31 | Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes |
| CA002277956A CA2277956C (en) | 1997-01-31 | 1998-01-29 | Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002277956A Division CA2277956C (en) | 1997-01-31 | 1998-01-29 | Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2692302A Division CA2692302C (en) | 1997-01-31 | 1998-01-29 | Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2564120A1 true CA2564120A1 (en) | 1998-08-06 |
| CA2564120C CA2564120C (en) | 2010-04-13 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2564120A Expired - Lifetime CA2564120C (en) | 1997-01-31 | 1998-01-29 | Method for utilizing neutral lipids to modify in vivo release from multivesicular liposomes |
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| CA (1) | CA2564120C (en) |
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| EP1189597A1 (en) * | 1999-06-04 | 2002-03-27 | SkyePharma Inc. | Oil-core compositions for the sustained release of hydrophobic drugs |
| WO2013064837A1 (en) * | 2011-11-03 | 2013-05-10 | Isis Innovation Limited | Multisomes: encapsulated droplet networks |
| EP2813220A3 (en) * | 2010-04-09 | 2015-06-17 | Pacira Pharmaceuticals, Inc. | Method for formulating large diameter synthetic membrane vesicles |
| US9831010B2 (en) | 2012-10-25 | 2017-11-28 | Oxford University Innovation Limited | Hydrogel network |
| US10950376B2 (en) | 2012-10-25 | 2021-03-16 | Oxford University Innovation Limited | Droplet assembly method |
| US11213797B2 (en) | 2012-12-07 | 2022-01-04 | Oxford University Innovation Limited | Droplet assembly by 3D printing |
-
1998
- 1998-01-29 CA CA2564120A patent/CA2564120C/en not_active Expired - Lifetime
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| JP2003501376A (en) * | 1999-06-04 | 2003-01-14 | スカイファーマ インコーポレーテッド | Oil core compositions for sustained release of hydrophobic drugs |
| EP1189597A4 (en) * | 1999-06-04 | 2008-06-18 | Pacira Pharmaceuticals Inc | Oil-core compositions for the sustained release of hydrophobic drugs |
| EP1189597A1 (en) * | 1999-06-04 | 2002-03-27 | SkyePharma Inc. | Oil-core compositions for the sustained release of hydrophobic drugs |
| US10045941B2 (en) | 2010-04-09 | 2018-08-14 | Pacira Pharmaceuticals, Inc. | Method for formulating large diameter synthetic membrane vesicles |
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| US9724302B2 (en) | 2010-04-09 | 2017-08-08 | Pacira Pharmaceuticals, Inc. | Method for formulating large diameter synthetic membrane vesicles |
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| US9757336B2 (en) | 2010-04-09 | 2017-09-12 | Pacira Pharmaceuticals, Inc. | Method for formulating large diameter synthetic membrane vesicles |
| US9808424B2 (en) | 2010-04-09 | 2017-11-07 | Pacira Pharmaceuticals, Inc. | Method for formulating large diameter synthetic membrane vesicles |
| AU2012330894B2 (en) * | 2011-11-03 | 2017-07-13 | Oxford University Innovation Limited | Multisomes: encapsulated droplet networks |
| WO2013064837A1 (en) * | 2011-11-03 | 2013-05-10 | Isis Innovation Limited | Multisomes: encapsulated droplet networks |
| US10548852B2 (en) | 2011-11-03 | 2020-02-04 | Oxford University Innovation Limited | Multisomes: encapsulated droplet networks |
| US11406603B2 (en) | 2011-11-03 | 2022-08-09 | Oxford University Innovation Limited | Multisomes: encapsulated droplet networks |
| US11998642B2 (en) | 2011-11-03 | 2024-06-04 | Oxford University Innovation Limited | Multisomes: encapsulated droplet networks |
| US9831010B2 (en) | 2012-10-25 | 2017-11-28 | Oxford University Innovation Limited | Hydrogel network |
| US10950376B2 (en) | 2012-10-25 | 2021-03-16 | Oxford University Innovation Limited | Droplet assembly method |
| US10978218B2 (en) | 2012-10-25 | 2021-04-13 | Oxford University Innovation Limited | Hydrogel network |
| US11213797B2 (en) | 2012-12-07 | 2022-01-04 | Oxford University Innovation Limited | Droplet assembly by 3D printing |
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| CA2564120C (en) | 2010-04-13 |
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