Delivery of agents to inflamed tissues using folate-targeted liposomes

Abstract

The invention described herein pertains to folate-receptor targeted agents comprising therapeutic agents useful for the treatment of inflammatory disease, including folate-receptor targeted liposomes (folate-targeted liposomes) containing entrapped therapeutic agents and folate-receptor targeted dendrimers conjugated to therapeutic agents (folate-targeted dendrimer conjugates), useful for the treatment of inflammatory disease, including auto-immune disease, as well as to folate-targeted liposomes containing entrapped imaging agents and dendrimer conjugates conjugated to imaging agents, for use in the diagnosis and monitoring of treatment in such disease.

1 .- 11 . (canceled) 
     
     
         12 . A method treating an inflammatory disease in a subject in need thereof, the method comprising administering a folate-receptor targeted liposomal composition comprising a lipid bilayer and an anti-inflammatory agent entrapped in the lipid bilayer. 
     
     
         13 . (canceled) 
     
     
         14 . A composition comprising a folate-targeted liposomal composition comprising an imaging or visualizing agent as an entrapped agent and further comprising at least one pharmaceutically acceptable carrier or excipient, wherein the lipid bilayer of the liposomal composition is primarily composed of DSPC/cholesterol with a mol ratio of about 56:40 and, wherein the hydrophilic polymer of the folate targeting conjugate is a PEG having an average molecular weight of about 200-5000 in which the end groups, prior to attachment, are independently amino, hydroxy, thiol or carboxy; and wherein the folate targeting conjugate is present at about 0.01 mol % to about 1 mol % in the lipid bilayer. 
     
     
         15 . A method of using the composition of  claim 14  for diagnosis or monitoring the treatment of an inflammatory disease in an inflamed tissue region in the body in a subject in need thereof. 
     
     
         16 . A kit comprising the composition of  claim 14  and instructions for diagnosis or monitoring the treatment of an inflammatory disease. 
     
     
         17 - 30 . (canceled) 
     
     
         31 . The method of  claim 12 , wherein the lipid bilayer comprises a folate-targeting conjugate composed of (a) a lipid having a polar head group and a hydrophobic tail, (b) a hydrophilic polymer having a first end and a second end, said polymer attached at its first end to the head group of the lipid, and (c) a folate ligand (Fol) attached to the second end of the polymer, and wherein the folate ligand is a folic acid residue or an analog or derivative thereof, wherein the hydrophilic polymer of the folate targeting conjugate is a PEG having an average molecular weight of about 200-5000 in which the end groups, prior to attachment, are independently amino, hydroxy, thiol or carboxy; and wherein the folate targeting conjugate is present at about 0.01 mol % to about 1 mol % in the lipid bilayer. 
     
     
         32 . The method of  claim 31 , wherein the lipid bilayer further comprises a hydrophilic coating composed of (a) a lipid having a polar head group and a hydrophobic tail and (b) a hydrophilic polymer having a first end and a second end, said polymer attached at its first end to the head group of the lipid and optionally capped at its second end, wherein the hydrophilic coating is a polyethylene glycol (PEG), a polylactic acid (PLA), a polyglycolic acid (PGA) or a polyvinyl alcohol (PVA).