Abstract: The present invention provides cationic-polymer-lipid conjugates (CPLs) such as distal cationic-poly(ethylene glycol)-lipid conjugates which can be incorporated into conventional and stealth liposomes or other lipid-based formulation for enhancing cellular uptake. The CPLs of the present invention comprise a lipid moiety; a hydrophilic polymer; and a polycationic moiety. Method of increasing intracellular delivery of nucleic acids are also provided.

Abstract: The present invention provides cationic-polymer-lipid conjugates (CPLs) such as distal cationic-poly(ethylene glycol)-lipid conjugates which can be incorporated into conventional and stealth liposomes or other lipid-based formulation for enhancing cellular uptake. The CPLs of the present invention comprise a lipid moiety; a hydrophilic polymer; and a polycationic moiety. Method of increasing intracellular delivery of nucleic acids are also provided.

Abstract: Novel methods are provided for loading a weakly basic drug into liposomes utilizing an electoneutral transport system. In these methods, ionophores are utilized with liposomes having a metal ion gradient to facilitate the exchange of metal ions for protons. The transported metal ion will, in some embodiments, be complexed with a chelating agent which is present in the external media.

Abstract: Methods for the preparation of stable liposome formulations of protonatable therapeutic agents. The methods involve loading a therapeutic agent into preformed liposomes having a methylamine concentration gradient across the lipid bilayer of the liposomes. These methods provide liposome formulations which are more stable, more cost effective, and easier to prepare in a clinical environment than those previously available. The present invention also provides the pharmaceutical compositions prepared by the above methods, a kit for the preparation of liposome formulations of therapeutic agents, and methods for their use.