Lipid carrier compositions and methods for improved drug retention - Patents

Lipid carrier compositions and methods for improved drug retention

Agent: Morrison & Foerster LLP - San Diego, CA, US
Inventors: Murray Webb, Paul Tardi
Class: 424450000 (USPTO), A61K009/127 (Intl Class)
#20050118249
06/02/05

Liposomal compositions which have enhanced retention properties for biological agents are characterized by an intrasomal osmolarity of 500 mOSM/kg or less and by containing substantially no cholesterol. The liposomes comprise vesicle forming lipids along with aggregation preventing components, and typically have transition temperatures of 38? C. or higher.
TECHNICAL FIELD
[0002] This invention is directed to improving drug retention in lipid-based therapeutic carrier systems by maintaining low osmotic pressure of the internal aqueous medium.
DISCLOSURE OF THE INVENTION
[0020] This invention is based on the finding that liposomes substantially free of cholesterol provide increased systemic retention of biologically active agents contained therein when the internal medium of the liposomes has an osmolarity of less than 500 mOsm/kg or an osmotic differential from physiological saline equal to or less than 200 mOsm/kg. Liposomes substantially free of cholesterol exhibit unanticipated improvements in the retention of encapsulated contents following intravenous administration.
[0021] Preferably, the liposomes are large unilamellar vesicles (LUV). In one embodiment, they comprise a hydrophilic polymer(s) grafted onto the surface by conjugation to a vesicle-forming lipid. They contain components that prevent aggregation and surface-surface interactions, such as phosphatidylglycerol, phosphatidylinositol and/or PEG modified lipids. In one embodiment the liposomes have a transition temperature >38.degree. C.
[0022] As discussed herein, the invention provides liposomes having drug retention properties suitable for administration to mammals, and thus includes pharmaceutical formulations comprising the liposomes of the invention, along with at least one pharmaceutically acceptable carrier.
[0023] The invention also relates to methods of administering liposomes to a mammal, and methods of treating a mammal affected by, susceptible to, or suspected of being affected by a disorder (e.g., cancer). Methods of treatment and/or administration may optionally further comprise a step of selecting or identifying a mammal, preferably a human, affected by, susceptible to, or suspected of being affected by a disorder. Methods of treatment or of administration will generally be understood to comprise administering the pharmaceutical composition at a dosage sufficient to ameliorate said disorder or symptoms thereof.
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