The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development of a screening method to reliably identify binding agents that can be used to target drugs to specific tissues or cell types. Targeting drugs can increase their effectiveness and reduce their side effects, thus it is important to develop methods that can screen for binding agents that can be used to enhance drugs that would otherwise have systemic activity. Existing methods do not attempt to replicate the environment in which binding agents are used, therefore agents that appear promising in the lab often fail in the clinic. The screening method incorporates a nano-scale drug carrier (i.e., nanocarrier) into the screening process, so that binding agents attached to it that perform well during screening can be expected to perform well in practice. A reliable drug targeting system of the type proposed could have enormous commercial value. Some analysts believe nanocarriers will account for 40% of a $136 billion nanotechnology-enabled drug delivery market by 2021. Because the benefits of targeted drug delivery over equivalent non-targeted systems are expected to be substantial, targeted nanocarriers are expected to account for most of this vast market.
This SBIR project aims to produce a targeted drug delivery system that is a first-of-its-kind in situ target ligand screening procedure. Targeted drug delivery is one of the most promising strategies for optimizing drug efficacy with minimal side effects, but current screening techniques for identifying highly specific targeting ligands suffer two drawbacks: (1) they only detect individual, high-affinity binding ligands (whereas well-organized, controllable, multiple, low-affinity/high-affinity binding ligands used in plurality are thought to provide the optimal specificity and inhibition); and (2) the manner in which they present ligands during screening in no way approximates the way ligands are presented in a targeted drug formulation, which leads to a high failure rate. The method developed in this project remedies these issues by (a) producing a screening library that employs precisely controlled nanocarriers, each type decorated with a unique collection of identical targeting ligands, and (b) employing as a targeted delivery vehicle or inhibitor, the nanocarrier with the optimal preferential binding affinity for a given target as identified during screening. This is the first method for developing a targeted nanocarrier that employs this type of in situ ligand screening.
