Loading patent…
AssigneeZoneone Pharma, Inc.
InventorsMark E. HAYES, Charles O. NOBLE, Francis C. SZOKA, JR.
Estimating the term…
The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading capability is retained. The process is scalable and, in liposomes in which the lipid composition and remote loading agent are optimized, the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and prolonged drug retention when the liposome encapsulated drug is administered to a subject.
-20. (canceled)
A method of remotely loading a precipitate of a solid active agent across liposomal membranes of liposomes, into an internal aqueous medium of the liposomes, from an aqueous suspension comprising the precipitate of the solid active agent and the liposomes, the solid active agent having a water solubility of less than 2 mg/mL, the method comprising:
A method of remotely loading a precipitate of a solid active agent across liposomal membranes of liposome, into an internal aqueous medium of the liposomes, from an aqueous suspension comprising a precipitate of the solid active agent and the liposomes, the solid active agent having a water solubility of less than 2 mg/mL, the method comprising:
A method of remotely loading a precipitate of a solid active agent across a liposomal membranes of liposomes, into an internal aqueous medium of the liposomes, from an aqueous suspension comprising a precipitate of the solid active agent and the liposomes, the solid active agent having a water solubility of less than 2 mg/mL, the method comprising:
The method according to claim 28, wherein the liposomes are from about 40 nm to about 200 nm in diameter.
Dependencies are inferred from the claim text.