Combination of liposomal anti-cancer drugs and lysosome/endosome pH increasing agents for therapy

• When liposomes are taken up by cells, they tend to accumulate in acidic vesicles, such as endosomes or lysosomes.
• The release of the drug from the lysosomes is, therefore, critical for cytotoxicity; i.e., the desired effect of the drug.

• The invention involves a pharmaceutical composition comprised of liposomes encapsulating a cationic amphiphilic drug (with both hydrophobic and hydrophilic groups), together with a lysosome/endosome pH increasing agent such as chloroquine - both should be administered close in time to each other.
• More specifically, the invention is based on the finding that chloroquine enhanced the cytotoxicity and growth inhibition of liposomal chemotherapeutic agents.

• Combinations of amphipathic weak base drug and lysosome/endosome pH increasing agent were found to improve the cytotoxicity of liposomal drugs.

• It was found that the larger the amount of the liposomal drug taken up by cells (as in the case of folate-targeted liposomes), the greater the enhancing effect of cytotoxicity of chloroquine.
• Successful laboratory in vitro and in vivo experiments, mainly carried out with pegylated liposomal doxorubicin (Doxil/Caelyx, approved for the treatment of ovarian and breast cancer), proved the concept and opened the way towards advanced R&D program, including expanded animal trials.

• The global cancer therapeutics market is expected to reach $60.6 billion in 2011, with an annual growth rate of 24.1%

Patent pending Publication WO08038291