Camposomes™

Camptothecin is an antitumor alkaloid that is isolated from the bark and stem wood of Camptotheca acuminata, a small tree native to China. This compound displays unprecedented antitumor activities against leukemia, human colon cancer and a variety of solid tumor systems. In particular, it was discovered that camptothecin traps the cleavable complex between topoisomerase I and DNA. Camptothecin is a unique topoisomerase I inhibitor which, while very effective, is not yet completely understood. In addition to its potent anticancer activity, camptothecin inhibits the replication of HIV and other viruses.

The full therapeutic activity of camptothecin has been limited by poor water solubility and aqueous instability of the lactone ring moiety. Ring opening will cause loss of biological activity of this compound. Preferential binding of the biologically inactive carboxylate form with human serum albumin further hinders drug effectiveness. Administration of the soluble sodium salt of camptothecin has proved to be ineffective and has delayed the development of this potent anticancer compound. As a result of this, camptothecin analogs that exhibit a superior solubility profile while retaining antitumor activity are being developed. These goals are frequently at odds, as increased hydrophilicity engenders greater exposure to the deactivating aqueous environment. Several promising clinical candidates, such as topotecan, CPT-11, and 9-aminocamptothecin, have emerged; topotecan and CPT-11 have been approved by the FDA for colorectal and other cancers.

Water soluble camptothecin analogs have yet to prove as effective as the native compound and some of its hydrophobic analogs. Liposomes are a useful drug delivery system for solubilizing camptothecin, while retaining both its lactone ring and antitumor activity. Hydrophobic compounds are trapped inside the lipid bilayers, masking the drug’s toxic nature and permitting a biocompatible formulation to be administered.

Aphios has utilized its patented SuperFluids™ CFN technology (US Patent Nos. 5,554,382 and 5,776,486) to form nanosomes (small, uniform liposomes) of camptothecin called Camposomes™. Liposomes are microscopic vesicles of phospholipid bilayers comprised of single or multiple lipid bilayers. Most liposomes are non-toxic, non-antigenic and biodegradable in character since they have the molecular characteristics of mammalian cell membranes.

The US National Cancer Institute conducted in vivo testing of Camposomes™, which were formulated using Aphios’ SuperFluids™ CFN critical fluid injection technique. Camposomes™ had a size distribution centered at 100 nm (S.D. 35 nm). The camptothecin concentration of the liposomal solution produced was 1.1 mg/mL by HPLC assay. Four groups of 10 mice were implanted with lymphoma xenografts and given intravenous treatment. For the highest dose (11 mg/Kg) tested, 3 were found to be tumor-free (cured) after 69 days with no drug-related deaths.

Camposomes™ will improve the efficacy, reduce the toxicity, and improve the solubility and stability of this unique topoisomerase I inhibitor and anticancer drug. We are seeking strategic corporate partners to continue the development of Camposomes™.