Therapeutic liposome composition and method of preparation
AssigneeAlza Corporation
InventorsFrancis J. Martin, Samuel Zalipsky
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Abstract
A fusogenic liposome composition for delivering a liposome-entrapped compound into the cytoplasm of a target cell is described. The liposomes have an outer surface coating of chemically releasable hydrophilic polymer chains which shield hydrophobic polymers on the liposome outer surface. Release of the hydrophilic polymer chains exposes the hydrophobic polymers for interaction with outer cell membranes of the target cells to promote fusion of the liposome with the target cells. Also disclosed is a method for using the composition to deliver a compound to target cells, and a method for selecting suitable hydrophobic polymers for use in the composition.
Claims28
A liposome composition for fusion with a target membrane of a cell, liposome, or the like, comprising
- a suspension of liposomes designed for targeting to the target membrane, where each liposome contains
- a therapeutic agent entrapped in the liposomes,
- an outer liposome surface having a coating of chemically releasable hydrophilic polymer chains, and
- hydrophobic polymers on the liposome outer surface, said polymers being shielded by the hydrophilic polymer coating and exposed for fusion with said target membrane when the hydrophilic polymer coating is chemically released.
A method of delivering a compound to target cells in a subject, comprising
- parenterally administering to the subject, liposomes designed for reaching the target cells via the bloodstream, each liposome containing said compound in entrapped form and having an outer surface coating of chemically releasable hydrophilic polymer chains, and
- contacting the liposomes at the target cells with a chemical agent effective to release said chains forming said surface coating, thereby to expose hydrophobic polymers on the liposome outer surface for interaction with outer cell membranes of the target cells and promote fusion of the liposome with the target cells.
A method for screening a hydrophobic polymer for fusogenic activity with a target membrane, comprising
- adding to a suspension of target cells, a triblock copolymer composed of a segment of the hydrophobic polymer to be tested, and attached to each end of the polymer segment, through a chemically releasable bond, a hydrophilic polymer segment effective to solubilize the hydrophobic polymer segment in the suspension,
- releasing said hydrophilic polymers to expose said hydrophobic segments to said target cells;
- and
- analyzing said suspension for hemolysis of said target cells.
A polymer-lipid conjugate for use in promoting fusion between target membranes, comprising
- a first segment composed of a hydrophilic polymer;
- a second segment composed of a hydrophobic polymer, said second segment joined to said first segment by a chemically releasable bond;
- and
- attached to said second segment, a vesicle-forming lipid member.
Dependencies are inferred from the claim text.