Pieter Cullis

Our research efforts are directed towards gaining an understanding of membrane structure and function at the molecular level and using the information gained to therapeutic advantage. Particular interests concern investigations on the functional roles of lipids in membranes employing model membrane systems and the generation and use of appropriately engineered liposomal nanoparticulate (LN) systems to deliver conventional and genetic drugs.

Our interests in LN systems can be divided into three parts:

1. LN Delivery of siRNA: RNA interference is a very attractive strategy for the treatment of human disease; however the therapeutic applicability of siRNAs has been hampered by the ineffective intracellular delivery of functional siRNAs to target cells in vivo. A focus of our laboratory is the design of LN systems that are able to effectively deliver their contents intracellularly following systemic administration, thus enabling the therapeutic use of siRNA. One important aspect of this work is the design and characterization of novel cationic lipids. The challenge in this work is to develop LN systems that are stable when in the circulation but are able to destabilize biological membranes following arrival at target tissue.
2. LN Delivery of Immunostimulatory Drugs: In addition to passively accumulating at sites of inflammation and malignant disease, LN delivery systems are naturally taken up by cells of the immune system following systemic administration. For this reason, our research focuses on using LN to enhance the delivery of immunostimulatory oligodeoxynucleotides containing CpG motifs to antigen presenting cells. This work is aimed at stimulating the innate immune system to improve the potency of monoclonal antibodies in cancer therapy as well as developing more effective vaccine adjuvants for use against infectious and malignant disease.
3. LN Encapsulation of Conventional Chemotherapeutics: The aim of our research with respect to the encapsulation of conventional chemotherapeutics is to take advantage of the natural tendency of long-circulating LN systems to accumulate at tumour sites. Our research in this area focuses on designing LN delivery systems which have optimized circulation lifetimes, to allow for an increased concentration of drug at the tumour site, and optimized drug release characteristics, to maximize the benefits of providing local sustained release of cell cycle-specific drugs at the site of disease. In addition, we are investigating ways in which to extend the LN technology to drugs that currently are not amenable to loading and retention in LN systems in attempt to increase the therapeutic index of already established drugs. A liposomal formulation of doxorubicin (the most commonly employed anticancer drug) developed in this laboratory is currently in advanced clinical trials in the United States.