Grant: Operating Grant

Liposomes or liposomal nanoparticles (LNP) are small vesicles within which drugs such as anticancer drugs can be encapsulated. The therapeutic benefits of LNP as drug carriers rely on their ability to efficiently load and retain the drug in the carrier so that it is delivered to the disease site. This is readily achieved for drugs that are weak bases, which can be loaded into LNP at high concentrations in response to a transmembrane pH gradient. However, there are important drugs that do not have the weakly basic amino groups that are required for drug loading and cannot be stably encapsulated and retained in liposomes. We have recently developed a way to efficiently encapsulate hydrophobic, poorly water-soluble drugs into LNP and have demonstrated the validity of this approach for docetaxel, a major anticancer drug. This approach involves synthesis of weak base derivatives of the drug that can be loaded into, and retained by, LNP but which is converted back to the parent drug on release. The work to be conducted under the present grant will extend this approach to develop LNP formulation of the anticancer drug etoposide and immunosuppressive drugs. In addition, targeting information will be incorporated into the LNP to achieve LNP uptake into prostate cancer cells. It is anticipated that the targeted LNP formulations of docetaxel and etoposide will result in improved modalties for the treatment of prostate cancer, whereas LNP immunosupressants will have an improved therapeutic profile as compared to drugs currently used to prevent transplant rejection.