Aphios Corporation

Bryosomes™

Bryosomes™ are phospholipid nanosomes containing bryostatin-1, a protein kinase C antagonist that is isolated form the “sea moss,” Bugula neritina, found off the coast of California. This novel anticancer agent has entered more than 35 Phase I and II clinical trials by the National Cancer Institute (NCI) and others for melanomas, lymphomas and other cancers.

While in vitro studies have shown that bryostatin 1 is a potent anticancer agent, bryostatin 1 has not demonstrated any significant efficacy as a single agent in clinical trials. Bryostatin 1, however, has demonstrated significant synergistic chemotherapeutic effects with other anticancer agents such as Taxol™. Paclitaxel, the active ingredient of Taxol™, is a potent anti-mitotic agent and effective anticancer drug. Both compounds are very hydrophobic, and have dose-limiting adverse side effects.

Bryostatin 1 is currently administered intravenously at 25 µg/m2 in a PET formulation (60 % polyethylene glycol 400, 30 % ethanol and 10 % Tween 80). Myalgia is the most common adverse event, and appears to be dose limiting. Paclitaxel is commercially formulated in 50 % polyoxyethylated castor oil and 50 % dehydrated alcohol (Cremophor EL) to make Taxol™. The Cremophor EL vehicle can have serious side effects including severe hypersensitivity reactions. Taxol™ has also caused myelosuppression, peripheral neuropathy and other side effects that are dose and schedule related. Severe toxicity profiles and side effects limit the clinical efficacy of bryostatin 1 and paclitaxel. Alternative delivery techniques such as phospholipid nanosomes have been explored to improve the delivery and the therapeutic efficacy of these agents while reducing their toxicities.

Phsopholipid nanosomes are small uniform liposomes that are microscopic vesicles of phospholipid bilayers comprised of single or multiple lipid bilayers. Phsopholipid nanosomes are non-toxic, non-antigenic and biodegradable in character since they have the molecular characteristics of mammalian cell membranes. Compounds are trapped inside the lipid bilayers and/or aqueous core compartment. Encapsulation masks the hydrophobic (water insoluble) nature of the drugs, and permits aqueous, biocompatible formulations to be administered. Encapsulation also prolongs the drugs' circulation, and for cancer chemotherapy, increases the likelihood that the drug will reach and destroy cancer cells. Phsopholipid nanosomes encapsulated therapeutic drugs can potentially lead to: (i) enhancement of drug efficacy; (ii) reduction of drug toxicity level; (iii) improved drug stability and (iv) prolongation of therapeutic drug release in the body.