Development of long-circulating nanoparticles for targeted drug delivery applications

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Polymeric nanoparticles represent a promising platform for targeted drug delivery applications. The central challenge in administering polymeric nanoparticles in vivo lies in the rapid particle clearance from the systemic circulation by the liver and spleen. As a result, only a small fraction of the administered nanoparticle dose is able to reach the targeted diseased cells and tissues. The nanoparticle clearance process is initiated when blood plasma proteins bind to the particle surface, making them visible to macrophages. The central aim of the proposed grant is to establish an active research program for developing drug-loaded polymeric nanoparticles that can effectively minimize plasma protein adsorption on the particle surface. It is hypothesized that the rate of nanoparticle clearance by macrophages can be substantially decreased by systemically optimizing the surface properties of polymeric nanoparticles. Our strategy involves modifying particle surfaces with natural polymers that mimic the protein-repelling surface properties of invasive pathogens. In the first phase of the proposed five-year research program, a platform technology will be developed for synthesizing self-assembled polymeric nanoparticles for targeted drug delivery. The second phase of the program will focusing on controlling the nanoparticle physicochemical properties to minimize protein adsorption on the particle surface. The nanoparticles developed from the proposed program may be used for a variety of clinical and biomedical applications. It is generally understood that targeted drug delivery holds great promise in pharmaceutical innovation for its ability to increase the effectiveness of existing drugs, decrease the necessity and thus cost for surgery and hospitalization and increase the quality of life of patients. The successful completion of the proposed NSERC discovery grant will help to secure Canada's position in nanobiotechnology and targeted drug delivery.