Lipid mediated screening of drug candidates for identification of active compounds
OwnerSean Michael Sullivan, Robert A. Copelandinventors
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Abstract
The subject invention provides liposome formulations that are capable of specifically targeting cell types. The subject invention also provides for the encapsulation of new chemical entities (NCE) or other drug candidate molecules (DCM) within liposomes that specifically target a particular cell type. The subject invention, advantageously, solubilizes compounds, with low solubility in aqueous environments, and permits screening of these compounds against intact cells for biological activity in the absence of detergents that can damage cell membranes. Also provided are methods of preparing liposome formulations that target a specific cell type and methods of delivering therapeutic agents to target cells.
Claims25
A method of screening active agents for biological effects on a target cell comprising:
- a) contacting a target cell with said cell-type specific liposomes (CTSL) optimized for said target cell comprising an encapsulated active agent selected from the group consisting of NCE;
- DCM;
- small molecules;
- agonists;
- antagonists;
- peptides;
- proteins;
- and nucleic acids selected from the group consisting of interfering RNA and antisense RNA;
- and
- b) assaying said cells for biological effects associated with said active agents.
A method of making cell-type specific liposomes (CTSL) comprising:
- a) combining, to form a suspension, water, ethanol, active agents/marker substances, additional components (AC) selected from the group consisting of phosphatidylglycerol, phosphatidylethanolamine, phosphatidic acid, phosphatidylinositol, monoglycerides, diglycerides, triglycerides, gangliosides, sphingomyelin, cerebrosides and combinations thereof to a standard liposome (SL) formulation that comprises:
- 1) phosphatidylcholine (PC) and cholesterol (Chol) in a PC:Chol ratio of about 2:1;
- or 2) diolcoylphosphatidylcholine (DOPC) and cholesterol (Chol) in a DOPC:Chol ratio of about 2:1;
- b) drying the suspension under vacuum;
- c) rehydrating the dried suspension with an isotonic solution;
- and
- d) assaying the rehydrated suspension for uptake of a marker substance by a target cell.
A method of treating an individual comprising the administration of a composition comprising a carrier and cell-type specific liposomes (CTSL) containing one or more therapeutic agent to an individual in an amount effective to treat the individual.
Dependencies are inferred from the claim text.