Novel liposome compositions

Abstract

The present disclosure provides lipid-containing compositions, including targeted liposomes encapsulating drug, and pharmaceutical formulations thereof, as well as methods for the making and using the lipid-containing compositions, including the use of the targeted liposomes in the treatment of cancer and other diseases.

1 . A targeted liposome comprising one or more phosphatidylcholines is DOPC or DSPC, an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, an encapsulated drug and, at least one additional lipid, which is cholesterol;
 wherein the mol % of the one or more phosphatidylcholines is 30-70 mol %; 
 wherein the targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine comprises a transferrin linked to a second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine; and 
 wherein 
 the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1, 
 
       
         
           
           
               
               
           
         
       
       and
 the second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 3, 
 
       
         
           
           
               
               
           
         
         
           wherein R 1 , R 2 , R 5  and R 6  are each an acyl group, 
           wherein the acyl groups are acyl groups from saturated or unsaturated aliphatic carboxylic acids having 16-18 carbon atoms, 
           wherein R 1 , R 2 , R 5  and R 6  are the same; and 
           m and p are equal and are an integer from 2 to 4; and; 
         
         wherein the targeted liposome contains from about 10 μg transferrin/mg lipid to about 50 μg transferrin/mg lipid; and, 
         wherein the liposome does not comprise a non-derivatized phosphatidyl ethanolamine, egg phosphatidylcholine or a hydrophilic polymer. 
       
     
     
         2 - 15 . (canceled) 
     
     
         16 . The targeted liposome according to  claim 1 , wherein the transferrin is in a holo-form but not in an apo-form. 
     
     
         17 . The targeted liposome according to  claim 1 , wherein the mean diameter of the liposome is from about 50 nm to about 250 nm. 
     
     
         18 . The liposome of  claim 1 , wherein R 1 , R 2 , R 5  and R 6  are oleoyl or stearoyl, and m and p are 3. 
     
     
         19 . The targeted liposome of  claim 18 , wherein the one or more phosphatidylcholine is DOPC. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . The targeted liposome of  claim 1 , wherein m and p are 3. 
     
     
         23 . The targeted liposome of  claim 1 , wherein R 1 , R 2 , R 5  and R 6  are oleoyl, stearoyl, or palmitoyl. 
     
     
         24 - 30 . (canceled) 
     
     
         31 . The targeted liposome according to  claim 1 , wherein the drug is an anticancer agent. 
     
     
         32 . The targeted liposome according to  claim 1 , wherein the drug is a cytotoxic drug. 
     
     
         33 . The targeted liposome according to  claim 1 , wherein the drug is a topoisomerase I inhibitor. 
     
     
         34 . The targeted liposome according to  claim 33 , wherein the topoisomerase I inhibitor is topotecan or irinotecan. 
     
     
         35 . The targeted liposome according to  claim 1 , wherein the drug is a vinca alkaloid. 
     
     
         36 . The targeted liposome according to  claim 35 , wherein the vinca alkaloid is vincristine, vinblastine, vinleurosine, vinrodisine, vinorelbine or vindesine. 
     
     
         37 . The targeted liposome according to  claim 1 , wherein the drug is a nucleic acid. 
     
     
         38 . The targeted liposome according to  claim 37 , wherein the nucleic acid is an antisense oligonucleotide or a ribozyme. 
     
     
         39 . The targeted liposome according to  claim 1 , wherein the drug is a platinum compound. 
     
     
         40 . The targeted liposome according to  claim 39 , wherein the platinum compound is biplatin, cisplatin, carboplatin, ormaplatin, oxaliplatin, zeniplatin, enloplatin, lobaplatin or spiroplatin. 
     
     
         41 . The targeted liposome according to  claim 40 , wherein the platinum compound is oxaliplatin. 
     
     
         42 . (canceled) 
     
     
         43 . The targeted liposome according to  claim 1 , wherein the drug is an alkylating agent. 
     
     
         44 . The targeted liposome according to  claim 1 , wherein the drug is a taxane. 
     
     
         45 . The targeted liposome according to  claim 1 , wherein the drug is a metabolic antagonist. 
     
     
         46 . The targeted liposome according to  claim 1 , wherein the drug is an antitumour antibiotic. 
     
     
         47 . The targeted liposome according to  claim 1 , wherein the drug is a hormone therapy drug. 
     
     
         48 . The targeted liposome according to  claim 1 , wherein the drug is a molecular target drug. 
     
     
         49 . The targeted liposome according to  claim 41 , wherein the oxaliplatin is dissolved in an aqueous solution of a sugar selected from the group consisting of trehalose, maltose, sucrose, mannose, lactose, mannitol, glycerol and dextrose. 
     
     
         50 . The targeted liposome of  claim 49 , wherein the sugar is at a concentration of from about 1 to about 20% percent sugar (v/v). 
     
     
         51 . The targeted liposome of  claim 41 , wherein the concentration of oxaliplatin is from about 0.1 mg/ml to about 25 mg/ml within the liposome. 
     
     
         52 . (canceled) 
     
     
         53 . The targeted liposome  claim 1 , wherein the liposome does not comprise a cationic lipid. 
     
     
         54 . The targeted liposome of  claim 1 , wherein the liposome does not comprise an anionic lipid. 
     
     
         55 - 254 . (canceled) 
     
     
         255 . The targeted liposome of  claim 1 , wherein the mol % of the second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is 0.5-2.5 mol %. 
     
     
         256 . The targeted liposome of  claim 1 , wherein the mol % of the one or more phosphatidylcholines is 35-55 mol %. 
     
     
         257 . The targeted liposome of  claim 1 , wherein R 1 , R 2 , R 5  and R 6  are oleoyl or stearoyl.