Development of Bacterial Mechanosensitive Channels as Nanodevices in Liposome Systems for Targeted Drug Delivery (2007–2009)
Liposomes are among the most advanced mainstream particulate drug carriers in modern medicine. They vary in complexity, but in their most basic form consist of naturally occurring phospholipid vesicles, capable of encapsulating a wide range of drugs. Such liposomes provide a high degree of biocompatibility and a physical barrier that protects the drug cargo from degradative enzymes in the patient. Furthermore, liposomes provide an effective, non-toxic method to solubilise hydrophobic drugs and administer potent and even highly toxic drugs such as the anthracyclines, Doxorubicin and Daunorubicin (clinically approved anti-cancer treatments), Amphotericin B (fungal disease therapy) and Taxol (cancer therapy).The focus of this project is to incorporate nanovalves into these drug delivery systems, in the form of bacterial mechanosensitive (MS) channels, to facilitate the controlled and rapid release of encapsulated drugs at targeted tumours or disease tissues. The successful completion of this project represents a significant advance on existing liposomal drug delivery systems because MS channels open and release the drug into or onto the target cell immediately following liposome binding. Liposomal drug delivery systems offer the additional advantages that they concentrate the drug inside the target tissue, thereby increasing its efficacy; reduce the exposure of healthy cells to toxic drugs; and increase safety to patients through loading site-specific drugs into site-directed liposomes. Specifically this project will develop:
1. Liposome formulations in which the MS channels are closed, but poised to open upon binding to the target cell.
2. Customised MS channels designed to optimize controlled release.
3. Structural information that will assist in the treatment of channelopathies linked to MS channels, i.e. diseases resulting from defects in MS ion channel function (e.g. muscular dystrophy, cardiac arrhythmias, autosomal-dominant polycystic kidney disease).