Pharmacokinetics of Targeted Nanoparticles

We are also working to develop a nanoparticle informatics resource that includes a comprehensive taxonomical database of available nanoparticle technologies and a general toolbox for pharmacokinetics and pharmacodynamics modeling of targeted drug delivery and diagnostics using nanoparticles. The NCI has recently identified nanotechnology and nanoparticle based drug delivery as an area of emphasis in its stated goal of eliminating cancer by the year 2015. In order for nanoparticle based drug delivery systems to be used effectively, we must therefore have a good understanding of the pharmacological properties of both the drugs and the nanoparticles being utilized.

We have access to reams of data pertaining to the biodistribution and toxicity of drugs. However a detailed knowledge of nanoparticle disposition is currently lacking. Our nanoinformatics resource is being developed in collaboration with two other computational biologists (Nathan Baker and Rohit Pappu , both Washington University). It collates information relevant to the pharmacological behavior of these nanoparticles, including the uptake, degradation and clearance of these particles, as well as the ability to conjugate each particle with binding ligands and small molecules or drugs. Additionally, the resource incorporates general pharmacokinetics and pharmacodynamics models to simulate the workings of nanoparticles as drug delivery agents.

One of our basic three-compartment schemes for modeling the distribution and release of nanoparticle bound drugs is shown above. Such models will allow us determine the vital factors in designing nanoparticles as drug carriers, and should eventually open the door to personalized medicine where the drugs, dosage and delivery can be customized and monitored for each individual patient. All of these elements will be combined into a web-based, publicly accessible database that will be directly connected to NCI's caBIG resource. Primary experimental data is being collected in collaboration with Greg Lanza and Sam Wickline (both Washington University School of Medicine).