Nanoparticulate compositions for targeted delivery of acid labile, lipophilic prodrugs of cancer chemotherapeutics and their preparation

A method for the treatment of cancer in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of the stable, synthetic low density lipoprotein (LDL) nanoparticle comprising:

• a) a lipophilic anti-cancer agent of the formula 1a, 1b or formula 2a:
• wherein:
• for formula 1a or 1b R1 is hydrogen, C1-C4 alkyl or C5-C22 alkyl;
• and R2 is C5-C22 alkyl;
• for formula 2a:
• R2 is C1-C22 alkyl;
• and X is hydrogen or is selected from the group consisting of Cl, Br and I;
• and
• R is a hydroxyl bearing cancer chemotherapeutic agent (HBCCA) selected from the group consisting of paclitaxel and docetaxel;
• b) phospholipids (PL) wherein the phospholipid is selected from the group consisting of phosphotidylcholine, phosphotidylethanolamine, symmetric or asymmetric 1,2-diacyl-sn-glycero-3-phosphorylcholines, 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine, 1,2-dimyristoyl-sn-glycero-3-phosphorylethanolamine, egg phospholipids, egg phosphatidyl glycerol, dipalmitoylphosphatidyl glycerol, egg lecithin, soy lecithin, lecithin (NOS) and mixtures thereof;
• and
• c) triglycerides (TG);
• wherein the LDL nanoparticle has a mean particle size of 40-80 nm;
• wherein the cancer is breast cancer.