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|Title:||Multivesicular liposomes utilizing neutral lipids to modify in vivo release|
|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 display 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.|
|Inventor(s):||Willis; Randall C. (Solana Beach, CA)|
|Assignee:||DepoTech Corporation (San Diego, CA)|
1. A multivesicular liposome for release of a biologically active compound comprising:
a neutral lipid component having a molar ratio of a slow release neutral lipid to a fast release neutral lipid in the range from about 1:1 to 1:100, wherein the slow release neutral lipid is selected from the group consisting of triolein, tripalmitolein, trimyristolien, trilaurin, tricaprin, and mixtures thereof, and the fast release neutral lipid is selected from the group consisting of tricaprylin, tricaproin, and mixtures thereof;
an amphipathic lipid; and
a biologically active compound encapsulated in water in the liposome.
2. The liposome of claim 1, wherein the melting point of the neutral lipid component is about or below 37.degree. C.
3. The liposome of claim 1, wherein the molar ratio of the neutral lipid component to all the lipids in the liposome is in the range from about 0.01 to about 0.21.
4. The liposome of claim 1, wherein the molar ratio of the slow release neutral lipid to the fast release neutral lipid is in the range from about 1:1 to 1:27.
5. The liposome of claim 1, wherein the molar ratio of the slow release neutral lipid to the fast release neutral lipid is in the range from about 1:1 to 1:18.
6. A method for administering a biologically active compound at a desired release rate comprising administering the liposome of claim 1 to a subject in need of the biologically active compound encapsulated therein.
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